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Hamdy NM, Barakat BM, El-Sisi MG, Shaker FH, Sallam AAM, Elazazy O, Darwish SF, Elmakromy GM, Ibrahim IH, Anwar MM. Comprehensive review and in silico analysis of the role of noncoding RNAs in retinoblastoma: A step-toward ncRNA precision. Int J Biol Macromol 2025; 311:144036. [PMID: 40345278 DOI: 10.1016/j.ijbiomac.2025.144036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 05/04/2025] [Accepted: 05/06/2025] [Indexed: 05/11/2025]
Abstract
Noncoding RNAs (ncRNAs) have greatly revolutionized our understanding of gene regulation and its main role in oncogenesis, particularly in retinoblastoma (RB), the most prevalent type of intraocular malignancy in children. Despite recent significant therapeutic advances, the prognosis for RB remains unclear owing to late diagnosis and resistance to conventional treatments. This review comprehensively explores the multiple roles of ncRNAs-microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs)-in RB pathogenesis. miRNA dysregulation serves as the initial cascade for modulating cell proliferation, apoptosis, and metastasis. Similarly, lncRNAs demonstrate dual behavior, functioning either as oncogenic drivers or tumor suppressors by interacting with several molecular targets and interacting with different signaling pathways, such as the PI3K/Akt and Wnt/β-catenin pathways. Additionally, circRNAs, owing to their persistent stability and unique ability to act as miRNA sponge main binding sites, affect various normal physiological processes, influencing tumor progression and chemoresistance. Emerging data also highlight the intricate crosstalk between piRNAs and other ncRNAs in retinal homeostasis and oncogenesis, with promising future implications for their utility as diagnostic biomarkers in liquid biopsy types. This comprehensive review consolidates the latest knowledge on the molecular mechanisms of noncoding RNAs (ncRNAs) in retinoblastoma (RB), along with in silico analysis of ncRNA-gene interactions, providing a guide for precision medical approaches. However, future research should aim to utilize ncRNAs as a vital clinical tool to improve the early diagnosis, prognosis, and targeted treatment of RB.
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Affiliation(s)
- Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566 Cairo, Egypt.
| | - Bassant M Barakat
- Department of Clinical Pharmacy, Faculty of Pharmacy, Al Baha University, Al Baha 1988, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11651, Egypt
| | - Mona G El-Sisi
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566 Cairo, Egypt
| | - Fatma H Shaker
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566 Cairo, Egypt
| | - Al-Aliaa M Sallam
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566 Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ola Elazazy
- Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Samar F Darwish
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Gena M Elmakromy
- Internal Medicine Department, Faculty of Medicine, Badr University In Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Iman Hassan Ibrahim
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Mai M Anwar
- Department of Biochemistry, National Organization for Drug Control and Research (NODCAR)/Egyptian Drug Authority (EDA), Cairo, Egypt
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Liu YY, Zhang YY, Ran LY, Huang B, Ren JW, Ma Q, Pan XJ, Yang FF, Liang C, Wang XL, Wang SM, Ran A, Ning H, Jiang Y, Qin CH, Xiao B. A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc. J Transl Med 2024; 22:507. [PMID: 38802851 PMCID: PMC11129431 DOI: 10.1186/s12967-024-05225-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/22/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.
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Affiliation(s)
- Yu-Ying Liu
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Yu-Ying Zhang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Ling-Yu Ran
- Department of Kidney, Southwest Hospital, Army Medical University, Chongqing, 400038, P.R. China
| | - Bo Huang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Jun-Wu Ren
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Qiang Ma
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Xiao-Juan Pan
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Fei-Fei Yang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Ce Liang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Xiao-Lin Wang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Shi-Min Wang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Ai Ran
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Hao Ning
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Yan Jiang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Chang-Hong Qin
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China
| | - Bin Xiao
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China.
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Zhang Y, Wang X, Liu W, Lei T, Qiao T, Feng W, Song W. CircGLIS3 promotes gastric cancer progression by regulating the miR-1343-3p/PGK1 pathway and inhibiting vimentin phosphorylation. J Transl Med 2024; 22:251. [PMID: 38459513 PMCID: PMC10921581 DOI: 10.1186/s12967-023-04625-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 10/13/2023] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated. METHODS The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional experiments in vitro and in vivo were performed to evaluated the effects of circGLIS3 on tumor growth and metastasis in GC. The interaction and regulation of circGLIS3/miR-1343-3p/PGK1 axis was confirmed by RNA pulldown, western blot, and rescue experiments. RIP and western blot were performed to demonstrate the role of circGLIS3 in regulating phosphorylation of VIMENTIN. We then used qRT-PCR and co culture system to trace circGLIS3 transmission via exosomal communication and identify the effect of exosomal circGLIS3 on gastric cancer and macrophages. Finally, RIP experiments were used to determine that EIF4A3 regulates circGLIS3 expression. RESULTS CircGLIS3(hsa_circ_0002874) was significantly upregulated in GC tissues and high circGLIS3 expression was associated with advanced TNM stage and lymph node metastasis in GC patients. We discovered that overexpression of circGLIS3 promoted GC cell proliferation, migration, invasion in vitro and in vivo, while suppression of circGLIS3 exhibited the opposite effect. Mechanistically, circGLIS3 could sponge miR-1343-3p and up-regulate the expression of PGK1 to promote GC tumorigenesis. We also found that circGLIS3 reduced the phosphorylation of VIMENTIN at ser 83 site by binding with VIMENTIN. Moreover, it was proven that exosomal circGLIS3 could promote gastric cancer metastasis and the M2 type polarization of macrophages. In the final step, the mechanism of EIF4A3 regulating the generation of circGLIS3 was determined. CONCLUSION Our findings demonstrate that circGLIS3 promotes GC progression through sponging miR-1343-3p and regulating VIMENTIN phosphorylation. CircGLIS3 is a potential therapeutic target for GC patients.
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Affiliation(s)
- Yongxin Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaofeng Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenwei Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tianxiang Lei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tang Qiao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Feng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wu Song
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Pietrzak J, Świechowski R, Wosiak A, Wcisło S, Balcerczak E. ADAMTS Gene-Derived circRNA Molecules in Non-Small-Cell Lung Cancer: Expression Profiling, Clinical Correlations and Survival Analysis. Int J Mol Sci 2024; 25:1897. [PMID: 38339175 PMCID: PMC10855670 DOI: 10.3390/ijms25031897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/26/2024] [Accepted: 02/03/2024] [Indexed: 02/12/2024] Open
Abstract
The present study examines the relationship between circular RNA (circRNA) derived from three genes of the family a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs): ADAMTS6, ADAMTS9 and ADAMTS12 and the host gene expression in non-small-cell lung cancer (NSCLC) with regard to various clinical factors. Notably, an association was identified between ADAMTS12 expression and specific circRNA molecules, as well as certain expression patterns of ADAMTS6 and its derived circRNA that were specific to histopathological subtypes. The survival analysis demonstrated that a lower ADAMTS6 expression in squamous cell carcinoma was associated with extended survival. Furthermore, the higher ADAMTS9 expression was linked to prolonged survival, while the overexpression of ADAMTS12 was correlated with a shorter survival. These findings suggest that circRNA molecules may serve as potential diagnostic or prognostic biomarkers for NSCLC, highlighting the importance of considering molecular patterns in distinct cancer subtypes.
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Affiliation(s)
- Jacek Pietrzak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland; (J.P.); (R.Ś.); (A.W.)
- BRaIn Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
| | - Rafał Świechowski
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland; (J.P.); (R.Ś.); (A.W.)
- BRaIn Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
| | - Agnieszka Wosiak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland; (J.P.); (R.Ś.); (A.W.)
- BRaIn Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
| | - Szymon Wcisło
- Department of Thoracic, General and Oncological Surgery, Medical University of Lodz and Military Medical Academy Memorial Teaching Hospital of the Medical University of Lodz - Central Veteran Hospital, 90-542 Lodz, Poland;
| | - Ewa Balcerczak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland; (J.P.); (R.Ś.); (A.W.)
- BRaIn Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
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Zheng Y, Sukocheva O, Tse E, Neganova M, Aleksandrova Y, Zhao R, Chubarev V, Fan R, Liu J. MicroRNA-183 cluster: a promising biomarker and therapeutic target in gastrointestinal malignancies. Am J Cancer Res 2023; 13:6147-6175. [PMID: 38187051 PMCID: PMC10767355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/29/2023] [Indexed: 01/09/2024] Open
Abstract
Small non-coding RNAs (microRNA, miR), powerful epigenetic regulators, were found involved in the regulation of most biological functions via post-translational inhibition of protein expression. Increased expression of pro-oncogenic miRs (known as miR cancer biomarkers) and inhibition of pro-apoptotic miR expression have been demonstrated in different tumors. The recently identified miR-183 was found implicated in gastrointestinal tumor metabolism regulation. Elevated miR-183 expression and cancer-promoting effects were reported in esophageal and colorectal cancers, which was partially contradicted by controversial data observed in gastric cancers. Anti-cancer effect of miR-183 in gastric cancer cells was associated with the Bim-1 and Ezrin genes regulation. Many studies indicated that miR-183 can inhibit tumor suppressor genes in most cell lines, promoting tumor cell proliferation and migration. Increased miR-183 level results in the downregulation of FOXO1, PDCD4, and other tumor suppressor genes in gastrointestinal tumor cells. MiR-183 also influences the signaling of PI3K/AKT/mTOR, Wnt/β-catenin, and Bcl-2/p53 signaling pathways. Mir-183 inhibits apoptosis and autophagy, and promotes epithelial-to-mesenchymal transition, cancer cell proliferation, and migration. Accordingly, gastrointestinal cancer occurrence, development of chemoradiotherapy resistance, recurrence/metastasis, and prognosis were associated with miR-183 expression. The current study assessed reported miR-183 functions and signaling, providing new insights for the diagnosis and treatment of gastrointestinal malignancies.
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Affiliation(s)
- Yufei Zheng
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, Henan, China
| | - Olga Sukocheva
- Department of Hepatology, Royal Adelaide HospitalAdelaide, SA 5000, Australia
| | - Edmund Tse
- Department of Hepatology, Royal Adelaide HospitalAdelaide, SA 5000, Australia
| | - Margarita Neganova
- Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of SciencesSevernij Pr. 1, Chernogolovka 142432, Russia
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of SciencesAkad. Arbuzov St. 8, Kazan 420088, Russia
| | - Yulia Aleksandrova
- Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of SciencesSevernij Pr. 1, Chernogolovka 142432, Russia
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of SciencesAkad. Arbuzov St. 8, Kazan 420088, Russia
| | - Ruiwen Zhao
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, Henan, China
| | - Vladimir Chubarev
- Sechenov First Moscow State Medical University (Sechenov University)8-2 Trubetskaya St., Moscow 119991, Russia
| | - Ruitai Fan
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, Henan, China
| | - Junqi Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, Henan, China
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Liu X, Zeng L, Wang W, Li Z, Zhou S, Wang F, Wang Y, Du J, Ma X. Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC. Oncol Lett 2023; 26:435. [PMID: 37664656 PMCID: PMC10472046 DOI: 10.3892/ol.2023.14022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 07/14/2023] [Indexed: 09/05/2023] Open
Abstract
Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC. RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.
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Affiliation(s)
- Xiaoyan Liu
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
| | - Lili Zeng
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Wenlong Wang
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Zhipeng Li
- Department of Stomatology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang 314001, P.R. China
| | - Siyuan Zhou
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
| | - Fang Wang
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Yue Wang
- Department of Stomatology, Zibo Central Hospital, Zibo, Shandong 255000, P.R. China
| | - Jing Du
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Xiangrui Ma
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
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Wang J, Han C, Wang J, Peng Q. RNA helicase DDX5-induced circPHF14 promotes gastric cancer cell progression. Aging (Albany NY) 2023; 15:2525-2540. [PMID: 36996491 PMCID: PMC10120908 DOI: 10.18632/aging.204623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/21/2023] [Indexed: 04/01/2023]
Abstract
As a well-established member of a strongly conserved protein family, DDX5 binds to RNA helicase in a specific manner, which can regulate mRNA transcription, protein translation and synthesis and precursor messenger RNA processing or alternative splicing. The effects of DDX5 on carcinogenesis and cancer progression are increasingly evident. Circular RNAs (circRNAs), a novel group of functionally non-coding RNAs (ncRNAs) with disordered expression, are associated with various pathological processes (e.g., tumors). circRNA pattern and its function regulated by DDX5 have not yet been determined. According to our findings, DDX5 was dramatically upregulated for stomach cancer tissues, and its overexpression contributed to the cell growth and invasion of GC cells. Based on the analysis of genome-wide circRNAs conducted with circRNA sequencing, DDX5 induces a large number of circRNAs. Further to screen several circRNAs from PHF14 for function, it was found that circPHF14 was essential for the growth and tumorigenesis of DDX5-positive gastric cancer cells. These findings suggest that in addition to the messenger RNA and microRNA patterns, DDX5 also effects a circRNA pattern, as demonstrated by circPHF14. DDX5-induced circRNAs have been found to be of crucial importance for the growth of DDX5-positive gastric cancer cells, providing a new therapeutic target.
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Affiliation(s)
- Jia Wang
- Department of Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China
- Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi 046000, Shanxi, China
| | - Chunjie Han
- Department of Orthopaedics, Heji Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi, China
| | - Jinsheng Wang
- Key Laboratory of Esophageal Cancer Basic Research and Clinical Transformation, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi, China
- Department of Pathology, Changzhi Medical College, Changzhi 046000, Shanxi, China
| | - Qiu Peng
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China
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8
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Khan QH. Identification of Conserved and Novel MicroRNAs with their Targets in Garden Pea ( Pisum Sativum L.) Leaves by High-Throughput Sequencing. Bioinform Biol Insights 2023; 17:11779322231162777. [PMID: 37020501 PMCID: PMC10068972 DOI: 10.1177/11779322231162777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 02/18/2023] [Indexed: 04/03/2023] Open
Abstract
MicroRNAs (miRNAs) are single-stranded, endogenous, non-coding RNAs of 20–24 nucleotides that play a significant role in post-transcriptional gene regulation. Various conserved and novel miRNAs have been characterized, especially from the plant species whose genomes were well-characterized; however, information on miRNA in economically important plants such as pea ( Pisum sativum L.) is limited. In this study, I have identified conserved and novel miRNA in garden pea plant leaves samples along with their targets by analyzing the next generation sequencing (NGS) data. The raw data obtained from NGS were processed and 1.38 million high-quality non-redundant reads were retained for analysis, this tremendous quantity of reads indicates a large and diverse small RNA population in pea leaves. After analyzing the deep sequencing data, 255 conserved and 11 novel miRNAs were identified in the garden pea leaves sample. Utilizing psRNATarget tool, the miRNA targets of conserved and novel miRNA were predicted. Further, the functional annotation of the miRNA targets were performed using blast2Go software and the target gene products were predicted. The miRNA target gene products along with GO_ID (Gene Ontology Identifier) were categorized into biological processes, cellular components, and molecular functions. The information obtained from this study will provide genomic resources that will help in understanding miRNA-mediated post-transcriptional gene regulation in garden peas.
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Affiliation(s)
- Qurshid Hasan Khan
- Qurshid Hasan Khan, Department of Plant
Sciences, University of Hyderabad, Gachibowli, Hyderabad 500046, Telangana,
India.
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9
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Yuan Y, Zhang X, Fan X, Peng Y, Jin Z. The emerging roles of circular RNA-mediated autophagy in tumorigenesis and cancer progression. Cell Death Dis 2022; 8:385. [PMID: 36104321 PMCID: PMC9474543 DOI: 10.1038/s41420-022-01172-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 08/23/2022] [Accepted: 08/26/2022] [Indexed: 11/09/2022]
Abstract
AbstractCircular RNA (circRNA) is characterized by a specific covalently closed ring structure. The back-splicing of precursor mRNA is the main way of circRNA generation, and various cis/trans-acting elements are involved in regulating the process. circRNAs exhibit multiple biological functions, including serving as sponges of microRNAs, interacting with proteins to regulate their stabilities and abilities, and acting as templates for protein translation. Autophagy participates in many physiological and pathological processes, especially it plays a vital role in tumorigenesis and carcinoma progression. Increasing numbers of evidences have revealed that circRNAs are implicated in regulating autophagy during tumor development. Until now, the roles of autophagy-associated circRNAs in carcinoma progression and their molecular mechanisms remain unclear. Here, the emerging regulatory roles and mechanisms of circRNAs in autophagy were summarized. Furtherly, the effects of autophagy-associated circRNAs on cancer development were described. We also prospected the potential of autophagy-associated circRNAs as novel therapeutic targets of tumors and as biomarkers for cancer diagnosis and prognosis.
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Fei Q, Lin Y, Zhang M, Guo J, Liang Y. circ_0061265 competitively binds to microRNA-885-3p to promote the development of gastric cancer by upregulating AURKA expression. Cancer Cell Int 2022; 22:277. [PMID: 36064409 PMCID: PMC9446739 DOI: 10.1186/s12935-022-02646-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 06/30/2022] [Indexed: 12/24/2022] Open
Abstract
Background Circular RNAs (circRNAs) represent a class of newly identified transcripts that act as competing endogenous RNAs (ceRNAs) to modulate gene expression by competing for the shared microRNAs (miRNAs) in humans. In this study, we set out to investigate the role of the circRNA-miRNA-mRNA ceRNA network in gastric cancer (GC). Methods A differential analysis on GC-related circRNAs, miRNAs and mRNAs was performed utilizing the R language “limma” package, followed by GO and KEGG enrichment analyses. The Cytoscape visualization software was used to construct the circRNA-miRNA-mRNA ceRNA network. RT-qPCR, Western blot assay, immunohistochemistry, RNA pull down, RIP and dual luciferase gene reporter assay were conducted to verify the expression of the related circRNA, miRNA and mRNA and their interaction in GC tissues and cells. Results The bioinformatics analysis screened 13 circRNAs, 241 miRNAs and 7483 mRNAs related to GC. Ten DEmRNAs (AURKA, BUB1, CCNF, FEN1, FGF2, ITPKB, CDKN1A, TRIP13, KNTC1 and KIT) were identified from the constructed PPI network and module analysis, among which AURKA was the most critical. A circ_0061265-miRNA-885-3p-AURKA ceRNA network was constructed. In vitro cell experiment demonstrated significantly upregulated circ_0061265 and AURKA, but downregulated miR-885-3p in GC. Moreover, circ_0061265 promoted the occurrence of GC by competitively binding to miRNA-885-3p to regulate AURKA expression. Conclusion Our work validated that circ_0061265 may increase AURKA expression by competitively binding to miRNA-885-3p, thereby promoting GC development. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-022-02646-3.
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Affiliation(s)
- Qian Fei
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 11021, People's Republic of China
| | - Yuhe Lin
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 11021, People's Republic of China
| | - Mi Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 11021, People's Republic of China
| | - Jinshuai Guo
- Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China
| | - Yuan Liang
- Medical Oncology Department of Thoracic Cancer (2), Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China.
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11
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Liu H, Li Q, Qi H, Du F, Qiu Y. Identification of circular RNA_0000919 as a potential diagnostic and prognostic biomarker of tongue squamous cell carcinoma using circular RNA microarray and reverse transcription‑quantitative PCR analyses. Oncol Lett 2022; 24:270. [PMID: 35782902 PMCID: PMC9247670 DOI: 10.3892/ol.2022.13390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/25/2021] [Indexed: 11/26/2022] Open
Abstract
The present study aimed to identify differentially expressed (DE) circular RNAs (circRNAs/circs) using microarray analysis and to further explore the clinical significance of 10 candidate DEcircRNAs in patients with tongue squamous cell carcinoma (TSCC). A total of 60 patients with TSCC who underwent surgery were enrolled and five pairs of TSCC and adjacent (Ctrl) tissues were used for circRNA microarray analysis. Subsequently, the top five upregulated and downregulated DEcircRNAs were detected by reverse transcription-quantitative PCR (RT-qPCR) analysis in 60 pairs of tumor and Ctrl tissues, and their association with tumor features and overall survival (OS) was further analyzed. circRNA expression was used to differentiate TSCC from Ctrl tissues by principal component and heatmap analyses. A total of 134 upregulated and 67 downregulated DEcircRNAs were identified in TSCC tissues compared with Ctrl tissues. The DEcircRNAs were enriched in oncogenic signaling, including the ‘Wnt signaling pathway’ and the ‘MAPK signaling pathway’. The majority of DEcircRNAs exhibited several target microRNAs (miRNAs) in regulatory network analysis. These findings were validated by RT-qPCR analysis and the results demonstrated that the expression levels of 9/10 selected candidate DEcircRNAs (circ_0020048, circ_0000919, circ_0004525, circ_0002113, circ_0004029, circ_0004503, circ_0008752, circ_0002300 and circ_0001811) were dysregulated in TSCC tissues compared with Ctrl tissues. The expression levels of five DEcircRNAs (circ_0004503, circ_0008752, circ_0002300, circ_0020048 and circ_0000919) were associated with pathological grade or tumor clinical stage. Notably, only the expression levels of one DEcircRNA (circ_0000919) were associated with decreased OS. In conclusion, the present study indicated aberrant circRNA expression and potential circRNA-miRNA interactions in TSCC and identified circ_0000919 as a diagnostic and prognostic biomarker for TSCC management.
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Affiliation(s)
- Hongli Liu
- Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China
| | - Qi Li
- Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China
| | - Han Qi
- Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China
| | - Fengzhi Du
- Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China
| | - Yanli Qiu
- Department of Stomatology, Cangzhou Medical College, Cangzhou, Hebei 061001, P.R. China
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Wang G, Sun L, Wang S, Guo J, Xiao R, Li W, Qi W, Qiu W. Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma. Mol Med Rep 2022; 25:118. [PMID: 35137922 PMCID: PMC8855154 DOI: 10.3892/mmr.2022.12634] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/11/2022] [Indexed: 12/24/2022] Open
Abstract
Ferroptosis is a form of programmed cell death that participates in diverse physiological processes. Increasing evidence suggests that long noncoding RNAs (lncRNAs) regulate ferroptosis in tumors, including stomach adenocarcinoma (STAD). In the present study, RNA-sequencing data from The Cancer Genome Atlas database and ferroptosis-related markers from the FerrDb data resource were analyzed to select differentially expressed lncRNAs. Univariate and multivariate Cox regression analyses were performed on these differentially expressed lncRNAs to screen 12 lncRNAs linked with overall survival (OS) and 13 associated with progression-free survival (PFS). Subsequently, two signatures for predicting OS and PFS were established based on these lncRNAs. Kaplan-Meier analyses indicated that the high-risk group of patients with STAD had relatively poor prognosis. The areas under the receiver operating characteristic curves of the two signatures indicated their excellent efficacy in predicting STAD prognosis. In addition, the effect of the lncRNA LASTR on proliferation and migration in gastric cancer was confirmed and the relationship between LASTR and ferroptosis was initially explored through experiments. These results provide potential novel targets for tumor treatment and promote personalized medicine.
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Affiliation(s)
- Gongjun Wang
- Department of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Libin Sun
- Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Shasha Wang
- Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Jing Guo
- Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Ruoxi Xiao
- Department of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Wenqian Li
- Department of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Weiwei Qi
- Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Wensheng Qiu
- Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
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Song J, Yu S, Zhong D, Yang W, Jia Z, Yuan G, Li P, Zhang R, Li Y, Zhong G, Chen Z. The circular RNA hsa_circ_000780 as a potential molecular diagnostic target for gastric cancer. BMC Med Genomics 2021; 14:282. [PMID: 34838011 PMCID: PMC8627072 DOI: 10.1186/s12920-021-01096-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 10/08/2021] [Indexed: 01/01/2023] Open
Abstract
Background The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). Methods Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. Results A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. Conclusions The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.
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Affiliation(s)
- Jian Song
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China.
| | - Shuyong Yu
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Dunjing Zhong
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Weizhong Yang
- Department of Digestive Endoscopy, The Affiliated Second Hospital of Hainan Medical University, Haikou, 570100, China
| | - Zhen Jia
- Department of Anesthesiology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Guihong Yuan
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Ping Li
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Ronglin Zhang
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Yini Li
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Guobing Zhong
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
| | - Zhaowei Chen
- Department of Gastroenterology, The Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570123, China
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Xia D, Chen Z, Liu Q. Circ-PGC increases the expression of FOXR2 by targeting miR-532-3p to promote the development of non-small cell lung cancer. Cell Cycle 2021; 20:2195-2209. [PMID: 34494941 DOI: 10.1080/15384101.2021.1974788] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
This study was to explore the function of circular progastricsin (circ-PGC) in NSCLC. The histological morphology of tumor tissues was observed by hematoxylin and eosin (HE) staining. The expression of circ-PGC, miR-532-3p and forkhead box R2 (FOXR2) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The protein level of FOXR2 was checked by western blot. In functional analyses, cell viability, colony formation, cell apoptosis, cell migration and cell invasion were investigated using cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, wound healing assay and transwell assay. Besides, glycolysis metabolism was assessed by the levels of glucose consumption, lactate production and adenosine triphosphate (ATP) production. The predicted relationship between miR-532-3p and circ-PGC and FOXR2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The results showed that circ-PGC and FOXR2 were upregulated in NSCLC tissues and cells. Circ-PGC knockdown or FOXR2 knockdown inhibited NSCLC cell viability, colony formation, cell migration, invasion and glycolysis metabolism, and FOXR2 overexpression rescued these inhibitory effects caused by circ-PGC knockdown. MiR-532-3p harbored the same binding site with circ-PGC and FOXR2, and circ-PGC positively regulated FOXR2 expression by targeting miR-532-3p. The expression of β-catenin and c-Myc was decreased in cells after circ-PGC knockdown but recovered with miR-532-3p inhibition or FOXR2 overexpression. Circ-PGC downregulation also inhibited tumor growth in vivo. In conclusion, circ-PGC positively regulated FOXR2 expression by competitively binding to miR-532-3p, thereby promoting the development of NSCLC, and the Wnt/β-catenin signaling pathway might be activated by the circ-PGC/miR-532-3p/FOXR2 network.
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Affiliation(s)
- Daokui Xia
- Department of Cardiothoracic Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China
| | - Zhen Chen
- Department of Cardiothoracic Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China
| | - Quan Liu
- Department of Cardiothoracic Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China
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15
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Fang J, Chen W, Meng X. Downregulating circRNA_0044516 Inhibits Cell Proliferation in Gastric Cancer Through miR-149/Wnt1/β-catenin Pathway. J Gastrointest Surg 2021; 25:1696-1705. [PMID: 33140323 DOI: 10.1007/s11605-020-04834-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 10/17/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Circular RNAs (circRNAs) play important roles in the progression of gastric cancer (GC). The Wnt1/β-catenin pathway can promote the proliferation of GC cells. This study aimed to explore whether circRNA_0044516 can regulate the proliferation of GC cells by modulating the Wnt1/β-catenin pathway. METHODS The expression of circRNA_0044516, miR-149, Wnt1, and β-catenin in GC tissues or cells was detected by qRT-PCR and western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays, respectively. The interaction between circRNA_0044516 and miR-149 was determined by luciferase reporter and RNA pull-down assays. RESULTS Upregulated circRNA_0044516 was found in GC tissues and cell lines. Downregulating circRNA_0044516 inhibited the viability and promoted apoptosis of GC cells. CircRNA_0044516 targeted miR-149, and its downregulation elevated miR-149 level in GC cells. Mechanistically, silencing circRNA_0044516 reduced the protein level of Wnt1 and β-catenin through miR-149, and finally suppressed viability and contributed to apoptosis of GC cells. Moreover, circRNA_0044516 knockdown inhibited the tumor growth of HGC-27 cells in nude mice. CONCLUSIONS Our results indicated an important role of circRNA_0044516 in GC and elucidated that downregulation of circRNA_0044516 inhibits the proliferation of GC cells through miR-149/Wnt1/β-catenin.
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Affiliation(s)
- Jun Fang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, NO. 218 Jixi Rd, Hefei, 230022, Anhui Province, China.
| | - Wei Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, NO. 218 Jixi Rd, Hefei, 230022, Anhui Province, China
| | - Xiangling Meng
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, NO. 218 Jixi Rd, Hefei, 230022, Anhui Province, China
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16
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Dong Z, Liu Z, Liang M, Pan J, Lin M, Lin H, Luo Y, Zhou X, Yao W. Identification of circRNA-miRNA-mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer. J Transl Med 2021; 19:226. [PMID: 34049561 PMCID: PMC8161999 DOI: 10.1186/s12967-021-02903-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Background Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention in human tumor research. However, the identification and function of circRNAs are largely unknown in the context of gastric cancer (GC). This study aims to identify novel circRNAs and determine their action networks in GC. Methods A comprehensive strategy of data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology were conducted to discover novel circRNAs and to explore their potential mechanisms in GC. Promising therapeutic drugs for GC were determined by connectivity map (CMap) analysis. Results Six overlapped differentially expressed circRNAs (DECs) were screened from selected microarray and RNA-Seq datasets of GC, and the six DECs were then validated by sanger sequencing and RNase R treatment. Subsequent RT-qPCR analysis of GC samples confirmed decreased expressions of the six DECs (hsa_circ_0000390, hsa_circ_0000615, hsa_circ_0001438, hsa_circ_0002190, hsa_circ_0002449 and hsa_circ_0003120), all of which accumulated preferentially in the cytoplasm. MiRNA binding sites and AGO2 occupation of the six circRNAs were predicted using online databases, and circRNA–miRNA interactions including the six circRNAs and 33 miRNAs were determined. Then, 5320 target genes of the above 33 miRNAs and 1492 differently expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) database were identified. After intersecting the miRNA target genes and the 889 downregulated DEGs, 320 overlapped target genes were acquired. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these target genes were related to two critical tumor-associated signaling pathways. A protein–protein interaction network with the 320 target genes was constructed using STRING, and fifteen hubgenes (ATF3, BTG2, DUSP1, EGR1, FGF2, FOSB, GNAO1, GNAI1, GNAZ, GNG7, ITPR1, ITPKB, JUND, NR4A3, PRKCB) in the network were identified. Finally, bioactive chemicals (including vorinostat, trichostatin A and astemizole) based on the fifteen hubgenes were identifed as therapeutic agents for GC through the CMap analysis. Conclusions This study provides a novel insight for further exploration of the pathogenesis and therapy of GC from the circRNA-miRNA-mRNA network perspective. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02903-5.
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Affiliation(s)
- Zhijie Dong
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Zhaoyu Liu
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Min Liang
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Jinhui Pan
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Mingzhen Lin
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Hai Lin
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Yuanwei Luo
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Xinke Zhou
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
| | - Wenxia Yao
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
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Chen L, Ma G, Wang P, Dong Y, Liu Y, Zhao Z, Guo J, Liang H, Yang L, Deng J. Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes. Am J Cancer Res 2021; 11:1335-1346. [PMID: 33948361 PMCID: PMC8085875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/16/2021] [Indexed: 06/12/2023] Open
Abstract
Autophagy played a significant role in the development of cancer. In this study, we explored the value of autophagy-associated genes in gastric cancer. RNA sequencing and clinical information containing 375 gastric cancer and 32 normal tissues were gathered from the TCGA portal. Then we stochastically allocated the autophagy-associated genes (AAGs) to training and testing groups. Next, we screened the discrepantly expressed AAGs and the prognostic AAGs by Cox regression analysis and Lasso regression analysis. Afterwards, we structured the model by using the prognostic AAGs and plotted Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves to verify the performance of models in both groups. Besides, we utilized Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular mechanisms of AAGs in gastric cancer. Finally, we demonstrated discrepant expression of AAGs within gastric cancer and non-tumor tissues at protein level with immunohistochemistry. 28 discrepantly expressed AAGs were screened from the TCGA database which contained 375 gastric cancer and 32 non-tumor samples. Cox and Lasso regression analyses were performed in training group and then we got 5 prognostic AAGs to establish the prognostic model. The patients who had high risk possessed worse overall survival (OS) both in training group (5-year OS, 47.6% vs 23.1%; P < 0.0001) and test group (5-year OS, 49.2% vs 0%, P=0.019). The proportion under ROC curves (AUC) were significant both in training group and test group (5-year AUC, 0.736 vs 0.809). Through this study, we constructed a model for gastric cancer patients which may provide individual treatment and superior prognosis.
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Affiliation(s)
- Liqiao Chen
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Gang Ma
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Pengliang Wang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Yinping Dong
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Yong Liu
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Zhenzhen Zhao
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Jiamei Guo
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Han Liang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
| | - Liyuan Yang
- No. 966 Hospital of PLADandong 118000, Liaoning, P. R. China
| | - Jingyu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060, P. R. China
- Key Laboratory of Cancer Prevention and TherapyTianjin 300060, P. R. China
- Tianjin’s Clinical Research Center for CancerTianjin 300060, P. R. China
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Rophina M, Sharma D, Poojary M, Scaria V. Circad: a comprehensive manually curated resource of circular RNA associated with diseases. DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION 2021; 2020:5812714. [PMID: 32219412 PMCID: PMC7100626 DOI: 10.1093/database/baaa019] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 01/22/2020] [Accepted: 02/17/2020] [Indexed: 01/17/2023]
Abstract
Circular RNAs (circRNAs) are unique transcript isoforms characterized by back splicing of exon ends to form a covalently closed loop or circular conformation. These transcript isoforms are now known to be expressed in a variety of organisms across the kingdoms of life. Recent studies have shown the role of circRNAs in a number of diseases and increasing evidence points to their potential application as biomarkers in these diseases. We have created a comprehensive manually curated database of circular RNAs associated with diseases. This database is available at URL http://clingen.igib.res.in/circad/. The Database lists more than 1300 circRNAs associated with 150 diseases and mapping to 113 International Statistical Classification of Diseases (ICD) codes with evidence of association linked to published literature. The database is unique in many ways. Firstly, it provides ready-to-use primers to work with, in order to use circRNAs as biomarkers or to perform functional studies. It additionally lists the assay and PCR primer details including experimentally validated ones as a ready reference to researchers along with fold change and statistical significance. It also provides standard disease nomenclature as per the ICD codes. To the best of our knowledge, circad is the most comprehensive and updated database of disease associated circular RNAs. Availability: http://clingen.igib.res.in/circad/
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Affiliation(s)
- Mercy Rophina
- Genome Informatics Department, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, District-South Delhi, New Delhi-110025, India
| | - Disha Sharma
- Genome Informatics Department, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, District-South Delhi, New Delhi-110025, India.,Academy of Scientific and Innovative Research (AcSIR), AcSIR headquarters, CSIR-HRDC campus, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh -201002, India
| | - Mukta Poojary
- Genome Informatics Department, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, District-South Delhi, New Delhi-110025, India.,Academy of Scientific and Innovative Research (AcSIR), AcSIR headquarters, CSIR-HRDC campus, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh -201002, India
| | - Vinod Scaria
- Genome Informatics Department, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, District-South Delhi, New Delhi-110025, India.,Academy of Scientific and Innovative Research (AcSIR), AcSIR headquarters, CSIR-HRDC campus, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh -201002, India
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19
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Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/β-catenin signalling pathway. Clin Sci (Lond) 2021; 134:1821-1839. [PMID: 32633323 DOI: 10.1042/cs20191043] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 06/15/2020] [Accepted: 07/07/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear. METHODS The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/β-catenin signalling in GC cells. RESULTS circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT), and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the β-catenin signalling. CONCLUSION circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the β-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.
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20
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Xu Q, Liao B, Hu S, Zhou Y, Xia W. Circular RNA 0081146 facilitates the progression of gastric cancer by sponging miR-144 and up-regulating HMGB1. Biotechnol Lett 2021; 43:767-779. [PMID: 33496921 DOI: 10.1007/s10529-020-03058-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/10/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Recent studies have revealed that circular RNA (circRNA) plays a pivotal role in cancer development. The study aimed to investigate the role of circ_0081146 in gastric cancer (GC). RESULTS Circ_0081146 was upregulated in GC tissues and cells. Patients with high expression of circ_0081146 had a significantly reduced 5-year overall survival rate. Circ_0081146 knockdown restrained the growth, migration and invasion of GC cells in vitro as well as tumorigenesis in vivo. Circ_0081146 targeted miR-144 and HMGB1 was targeted by miR-144. Circ_0081146 was negatively correlated with miR-144 expression, while positively correlated with HMGB1 expression in GC tissues. Moreover, the inhibitory effect of circ_0081146 knockdown on the progression of GC cells were reversed by silencing miR-144 or HMGB1 overexpression. Mechanically, circ_0081146 increased HMGB1 expression by targeting miR-144. CONCLUSION Circ_0081146 functions as an oncogene in GC to promote cell growth, migration and invasion via modulating the miR-144/HMGB1 axis.
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Affiliation(s)
- Qihua Xu
- Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Pudong New Area, Shanghai, 200137, China
| | - Bingling Liao
- Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Pudong New Area, Shanghai, 200137, China
| | - Sheng Hu
- Department of Gastrointestinal Surgery, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Ying Zhou
- Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Pudong New Area, Shanghai, 200137, China.
| | - Wei Xia
- Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Pudong New Area, Shanghai, 200137, China.
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21
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Zhang Y, Hong Y, Wang D, Duan L, Liu Y, Li L, Liu D, Zhuang K, Wei C, Zheng G, Huo C, Liu G. Hsa_circ_0076305 induces migration-proliferation dichotomy in gastric cancer. Oncol Lett 2021; 21:220. [PMID: 33613709 PMCID: PMC7859472 DOI: 10.3892/ol.2021.12481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 11/13/2020] [Indexed: 12/27/2022] Open
Abstract
Recent studies have demonstrated that circular RNAs (circRNAs) play an important role in the development of gastric cancer (GC). The present study aimed to investigate the role of hsa_circ_0076305 (circPGC) in GC. The levels of circRNAs and mRNAs in AGS cell lines were detected via reverse transcription-quantitative PCR, and western blotting was performed to detect protein expression levels. Functional studies were explored by CCK8 assay and cell migration assay. Functional studies have indicated that circPGC orchestrates two cellular processes; it inhibits proliferation, and promotes migration and invasion in the GC AGS cell line, a phenomenon called ‘migration-proliferation dichotomy’, as well as epithelial-to-mesenchymal transition in AGS cells. In addition, circPGC degrades the extracellular matrix and basement membrane through matrix metallopeptidase (MMP)9 and MMP14, providing a microenvironment that facilitates cell migration. The results also demonstrated that circPGC expression is lower in clinical patients with later stages of GC, which is associated with poor prognosis. Taken together, these results suggest that circPGC exhibits migration-proliferation dichotomy during GC development, invasion and migration.
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Affiliation(s)
- Yuhai Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China.,Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Yuling Hong
- Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China.,Department of Cancer Prevention and Rehabilitation, Huayan Science and Technology Cancer Prevention and Rehabilitation Research Center, School of Pharmaceutical Sciences Xiamen University, Xiamen, Fujian 361102, P.R. China
| | - Dan Wang
- Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Linshan Duan
- Department of Cancer Prevention and Rehabilitation, Huayan Science and Technology Cancer Prevention and Rehabilitation Research Center, School of Pharmaceutical Sciences Xiamen University, Xiamen, Fujian 361102, P.R. China
| | - Yanling Liu
- Department of Cancer Prevention and Rehabilitation, Huayan Science and Technology Cancer Prevention and Rehabilitation Research Center, School of Pharmaceutical Sciences Xiamen University, Xiamen, Fujian 361102, P.R. China
| | - Long Li
- Department of Cancer Prevention and Rehabilitation, Huayan Science and Technology Cancer Prevention and Rehabilitation Research Center, School of Pharmaceutical Sciences Xiamen University, Xiamen, Fujian 361102, P.R. China
| | - Di Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China.,Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Kunbin Zhuang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China.,Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Chaoxin Wei
- School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350000, P.R. China
| | - Guogeng Zheng
- School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350000, P.R. China
| | - Chunyong Huo
- School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350000, P.R. China
| | - Guoyan Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China.,Department of Basic Medicine, Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China.,Department of Cancer Prevention and Rehabilitation, Huayan Science and Technology Cancer Prevention and Rehabilitation Research Center, School of Pharmaceutical Sciences Xiamen University, Xiamen, Fujian 361102, P.R. China.,School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350000, P.R. China.,College of Food an Biological Engineering, Jimei University, Xiamen, Fujian 361021, P.R. China
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22
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circ_0044516 functions in the progression of gastric cancer by modulating MicroRNA-149-5p/HuR axis. Mol Cell Biochem 2021; 477:2161-2171. [PMID: 33417162 DOI: 10.1007/s11010-020-04026-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 12/22/2020] [Indexed: 01/01/2023]
Abstract
Circular RNAs (circRNAs) have emerged as a multifunctional class of RNAs, while there is limited knowledge on their functions in the development of cancers. Herein, we performed the current study to probe into the regulatory mechanism of circ_0044516 in malignant behaviors of gastric cancer (GC) cells with the involvement of microRNA (miR)-149-5p/human antigen R (HuR) axis. Firstly, the expression levels of circ_0044516 in GC cell lines and normal gastric mucosal epithelial cells were determined by qRT-PCR, and GC cell lines with the highest expression of circ_0044516 were screened for further cell experiments. Subsequently, the biological functions of silenced circ_0044516 in GC were identified by CCK-8, colony formation, and transwell assays. Xenograft mouse models were established for in vivo verification. Furthermore, luciferase reporter, RIP, RNA pull-down assay and rescue experiments were performed to explore the sponge regulatory mechanism of circ_0044516. circ_0044516 was suggested to be highly expressed in GC cell lines, and circ_0044516 could promote GC cell proliferation, migration and invasion, as well as in vivo tumor growth. In addition, silenced circ-0044516 reversed the promotive roles in cell viability caused by overexpressed HuR. Furthermore, circ_0044516 mainly localized in the cytoplasm, which may act as a miR-149-5p sponge to modulate HuR expression, thereby playing an essential role in GC development. This study suggests that circ_0044516 may promote HuR expression through sponging miR-149-5p, thereby playing a part in GC progression.
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23
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Wang S, Tang X, Qin L, Shi W, Bian S, Wang Z, Wang Q, Wang X, Gu J, Hao B, Ding K, Liao S. Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome. Front Genet 2020; 11:565955. [PMID: 33329702 PMCID: PMC7735064 DOI: 10.3389/fgene.2020.565955] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 10/01/2020] [Indexed: 12/14/2022] Open
Abstract
Accumulating evidence suggests that circular RNAs (circRNAs)-miRNA-mRNA ceRNA regulatory network-may play an important role in neurological disorders, such as Alzheimer's disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21. Here, we characterized the expression profiles of circRNAs in the fetal hippocampus of DS patients (n = 8) and controls (n = 6) by using microarray. MiRNA, mRNA expression profiling of DS from our previous study and scRNA-seq data describing normal fetal hippocampus development (GEO) were also integrated into the analysis. The similarity between circRNAs/genes with traits/cell-types was calculated by weighted correlation network analysis (WGCNA). miRanda and miRWalk2 were used to predict ceRNA network interactions. We identified a total of 7,078 significantly differentially expressed (DE) circRNAs, including 2,637 upregulated and 4,441 downregulated genes, respectively. WGCNA obtained 15 hub circRNAs and 6 modules with cell type-specific expression patterns among scRNA-seq data. Finally, a core ceRNA network was constructed by 14 hub circRNAs, 17 DE miRNA targets and 245 DE mRNA targets with a cell type-specific expression pattern annotation. Known functional molecules in DS or neurodegeneration (e.g., miR-138, OLIG1, and TPM2) were also included in this network. Our findings are the first to delineate the landscape of circRNAs in DS and the first to effectively integrate ceRNA regulation with scRNA-seq data. These data may provide a valuable resource for further research on the molecular mechanisms or therapeutic targets underlying DS neuropathy.
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Affiliation(s)
- Shengran Wang
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Xia Tang
- Henan Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, Henan Provincial People's Hospital, Zhengzhou, China
| | - Litao Qin
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Weili Shi
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Shasha Bian
- School of Medicine, Henan University, Zhengzhou, China
| | - Zhaokun Wang
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Qingqing Wang
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Xin Wang
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Jianqin Gu
- School of Medicine, Henan University, Zhengzhou, China
| | - Bingtao Hao
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Keyue Ding
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
| | - Shixiu Liao
- Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Zhengzhou, China.,Henan Provincial People's Hospital, School of Medicine, Henan University, Zhengzhou, China
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24
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Wu W, Zhen T, Yu J, Yang Q. Circular RNAs as New Regulators in Gastric Cancer: Diagnosis and Cancer Therapy. Front Oncol 2020; 10:1526. [PMID: 33072546 PMCID: PMC7531269 DOI: 10.3389/fonc.2020.01526] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 07/16/2020] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC) is one of the most commonly diagnosed cancers that causes high mortality in the world. Although the surgery tools and chemotherapies have significantly improved the overall survival of patients with GC, the early diagnosis of GC remains insufficient and many patients diagnosed with advanced stages of GC are not able to benefit from curative therapy. Circular RNAs (circRNAs), novel members of the non-coding cancer genome, are being explored with regards to various cancer types including GC. CircRNAs could work as miRNA sponges to regulate cell proliferation, cell migration, and cell cycle in GC. In addition, it was found that abnormal expression of circRNAs was associated with pathological characteristics in GC tissues, which could help to act as potential markers of early diagnosis or predictors of prognosis. Although various functional circRNAs have been discovered and characterized, the studies of circRNAs in GC are still at early stages compared with other RNAs. In order to provide a whole view to better understand the circRNAs in the occurrence and development of GC, we review the current knowledge on circRNAs in relation to their expression and regulation in GC as well as their potential to be diagnosis markers, and their role in drug resistance will be mentioned. It is helpful to address their possibility from basic research into practical application.
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Affiliation(s)
- Wei Wu
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
- Institute for Translational Medicine, Qingdao University, Qingdao, China
| | - Tianyuan Zhen
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
| | - Junmin Yu
- Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Qingli Yang
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
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25
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Ding C, Xi G, Wang G, Cui D, Zhang B, Wang H, Jiang G, Song J, Xu G, Wang J. Exosomal Circ-MEMO1 Promotes the Progression and Aerobic Glycolysis of Non-small Cell Lung Cancer Through Targeting MiR-101-3p/KRAS Axis. Front Genet 2020; 11:962. [PMID: 33005174 PMCID: PMC7483554 DOI: 10.3389/fgene.2020.00962] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 07/31/2020] [Indexed: 12/28/2022] Open
Abstract
Circular RNA mediator of cell motility 1 (circ-MEMO1) was identified as an oncogene in non-small cell lung cancer (NSCLC). Nevertheless, the working mechanism behind circ-MEMO1-mediated progression of NSCLC is barely known. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-MEMO1, microRNA-101-3p (miR-101-3p), and KRAS proto-oncogene, GTPase (KRAS). Cell proliferation and aerobic glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and glycolysis detection kits. Flow cytometry was used to evaluate cell cycle progression and apoptosis of NSCLC cells. Western blot assay was used to measure the protein expression of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), KRAS, CD9, CD81, tumor susceptibility 101 (TSG101), and Golgi matrix protein 130 kDa (GM130). The target relationship between miR-101-3p and circ-MEMO1 or KRAS was predicted by StarBase software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. In vivo tumor growth assay was conducted to assess the effect of circ-MEMO1 in vivo. Exosomes were isolated using the ExoQuick precipitation kit. Circ-MEMO1 was up-regulated in NSCLC, and high expression of circ-MEMO1 predicted poor prognosis in NSCLC patients. Circ-MEMO1 accelerated the proliferation, cell cycle progression, and glycolytic metabolism and inhibited the apoptosis of NSCLC cells. Circ-MEMO1 negatively regulated the expression of miR-101-3p through direct interaction, and si-circ-MEMO1-induced biological effects were attenuated by the introduction of anti-miR-101-3p. MiR-101-3p directly interacted with the 3′ untranslated region (3′ UTR) of KRAS messenger RNA (mRNA), and KRAS level was regulated by circ-MEMO1/miR-101-3p axis. Circ-MEMO1 silencing suppressed the NSCLC tumor growth in vivo. ROC curve analysis revealed that high expression of serum exosomal circ-MEMO1 (exo-circ-MEMO1) might be a valuable diagnostic marker for NSCLC. Circ-MEMO1 facilitated the progression and glycolysis of NSCLC through regulating miR-101-3p/KRAS axis.
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Affiliation(s)
- Chengzhi Ding
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Gaoyuan Xi
- Department of Anesthesiology, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Guolei Wang
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Dong Cui
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Binbin Zhang
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Hongtao Wang
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Gongqian Jiang
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Jingchao Song
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Guanghui Xu
- Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China
| | - Jiao Wang
- Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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26
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Bhuyan R, Bagchi A. Prediction of the differentially expressed circRNAs to decipher their roles in the onset of human colorectal cancers. Gene 2020; 762:145035. [PMID: 32777531 DOI: 10.1016/j.gene.2020.145035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/14/2020] [Accepted: 08/04/2020] [Indexed: 12/17/2022]
Abstract
Circular RNAs belong to the class of endogenous long non-coding RNAs that play important roles in many physiological processes including tumorigenesis. One such process is the onset of colorectal cancers (CRC) which is one of the most prevalent cancers in the world. However, the involvement of the circRNAs in CRC progression is still obscure. In this study, we screened the differentially expressed circRNAs in CRC by taking 10 pairs of tumor and non-tumor transcriptomic data. Datasets were downloaded from EBI ENA database and differential expression analysis was performed. For functional characterization and pathway enrichment of differentially expressed circRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed. Interactions with miRNAs and RNA binding proteins (RBPs) were predicted using miRanda, miRTarBase and starBase tools respectively. Our results identified total of 122 differentially expressed circRNAs in CRC onset, including 85 upregulated and 37 downregulated. GO and KEGG analyses revealed these circRNAs to be involved in many tumorigenic pathways. In addition, we predicted many miRNA and RBP targets of significantly expressed circRNAs that could exhibit the functional role in CRC progression. Combined analyses of miRanda, miRTarBase and KEGG pathway suggested that the possibly affected genes by circRNA-miRNA sponge to be associated with many cancer related pathways. From our findings we concluded 16 novel differentially expressed circRNAs that could play important roles in carcinogenesis of CRC. Our findings provide new insights in circRNA research and could therefore be useful in the development of potential biomarker and therapeutic approaches for CRC.
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Affiliation(s)
- Rajabrata Bhuyan
- Department of BioScience and Biotechnology, Banasthali Vidyapith, Banasthali, 304022 Tonk, Rajasthan, India.
| | - Angshuman Bagchi
- Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia, 741235, India.
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27
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Wang GJ, Yu TY, Li YR, Liu YJ, Deng BB. Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway. Cancer Cell Int 2020; 20:351. [PMID: 32742198 PMCID: PMC7391524 DOI: 10.1186/s12935-020-01422-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/13/2020] [Indexed: 12/20/2022] Open
Abstract
Background Gastric cancer is a serious malignant tumor associated with aberrant circular RNAs (circRNAs) expression. In this study, we aim to investigate the role and the underlying mechanism of circ_0000190, a circRNA in gastric cancer. Methods Circ_0000190 expression in vivo was examined in gastric cancer and adjacent normal tissues by RT-PCR. Circ_0000190 expression in gastric cancer cell lines was detected by FISH and RT-PCR. The role of the circRNA in gastric cancer cells was assessed by the analysis of cell viability, apoptosis, proliferation, cell cycle and migration. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. Furthermore, Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190. Results Circ_0000190 was down-regulated in gastric cancer tissues and cells, with a major location in cytoplasm. Circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cell cycle arrest by regulating the expression of capase-3, p27 and cyclin D. In addition, the circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects of circ_0000190 on the cellular processes were blocked by miR-1252 mimics, which could be rescued after further overexpression of PAK3. Conclusions Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway, employing circ_0000190 might be a promising therapeutic strategy for the treatment of gastric cancer.
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Affiliation(s)
- Gui-Jun Wang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000 China
| | - Tian-Yu Yu
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000 China
| | - Yan-Rong Li
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000 China
| | - Yang-Jun Liu
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000 China
| | - Bei-Bei Deng
- Department of Clinical Laboratory, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, 121000 Liaoning China
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28
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Zhang C, Wang J, Geng X, Tu J, Gao H, Li L, Zhou X, Wu H, Jing J, Pan W, Mou Y. Circular RNA expression profile and m6A modification analysis in poorly differentiated adenocarcinoma of the stomach. Epigenomics 2020; 12:1027-1040. [PMID: 32657141 DOI: 10.2217/epi-2019-0153] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aims: To profile and characterize the circular RNA (circRNA) expression pattern in poorly differentiated gastric adenocarcinoma (PDGA). Methods & materials: CircRNA expression profiles in PDGA and adjacent nontumor tissues were analyzed by microarray. Five randomly selected differentiated expressed circRNAs (DECs) were validated by real-time quantitative PCR. m6A qualification of the top 20 DECs was conducted by m6A-immunoprecipitation and real-time quantitative PCR. Results: A total of 65 DECs were found in PDGA compared with the control. Hsa_circRNA_0077837 had the largest area under the curve. Most DECs had m6A modifications, the trend of m6A modification alteration was mainly consistent with the circRNA expression level. Conclusion: Our study revealed a set of DECs and their m6A modification alterations, which may provide new insight for their potential function in PDGA.
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Affiliation(s)
- Chenjing Zhang
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Jingya Wang
- Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Xiaoge Geng
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Jiangfeng Tu
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Huiqin Gao
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Lunan Li
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Xiaolu Zhou
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Hongguang Wu
- Department of Gastroenterology, the Second People's Hospital of Quzhou, Quzhou, Zhejiang, PR China
| | - Jiyong Jing
- Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, PR China
| | - Wensheng Pan
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, PR China
| | - Yiping Mou
- Department of Gastrointestinal & Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, PR China
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Tian J, Fu Y, Li Q, Xu Y, Xi X, Zheng Y, Yu L, Wang Z, Yu B, Tian J. Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells. Front Genet 2020; 11:530. [PMID: 32547599 PMCID: PMC7272660 DOI: 10.3389/fgene.2020.00530] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/01/2020] [Indexed: 12/24/2022] Open
Abstract
Atherosclerosis is mediated by various factors and plays an important pathological foundation for cardiovascular and cerebrovascular diseases. Abnormal vascular smooth muscle cells (VSMCs) proliferation and migration have an essential role in atherosclerotic lesion formation. Circular RNAs (circRNA) have been widely detected in different species and are closely related to various diseases. However, the expression profiles and molecular regulatory mechanisms of circRNAs in VSMCs are still unknown. We used high-throughput RNA-seq as well as bioinformatics tools to systematically analyze circRNA expression profiles in samples from different VSMC phenotypes. Polymerase chain reaction (PCR), Sanger sequencing, and qRT-PCR were performed for circRNA validation. A total of 22191 circRNAs corresponding to 6273 genes (host genes) in the platelet-derived growth factor (PDGF-BB) treated group, the blank control group or both groups, were detected, and 112 differentially expressed circRNAs were identified between the PDGF-BB treated and control groups, of which 59 were upregulated, and 53 were downregulated. We selected 9 circRNAs for evaluation of specific head-to-tail splicing, and 10 differentially expressed circRNAs between the two groups for qRT-PCR validation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses enrichment analyses revealed that the parental genes of the circRNAs mainly participated in cardiac myofibril assembly and positive regulation of DNA-templated transcription, indicating that they might be involved in cardiovascular diseases. Finally, we constructed a circRNA-miRNA network based on the dysregulated circRNAs and VSMC-related microRNAs. Our study is the first to show the differential expression of circRNAs in PDGF-BB-induced VSMCs and may provide new ideas and targets for the prevention and therapy of vascular diseases.
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Affiliation(s)
- Jiangtian Tian
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yahong Fu
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qi Li
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Pathology, Harbin Medical University, Harbin, China
| | - Ying Xu
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Basic Medical College of Mudanjiang Medical College, Mudanjiang, China
| | - Xiangwen Xi
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yuqi Zheng
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Li Yu
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhuozhong Wang
- Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.,Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Bo Yu
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jinwei Tian
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Ding Y, Dong Y, Lu H, Luo X, Fu J, Xiu B, Liang A, Zhang W. Circular RNA profile of acute myeloid leukaemia indicates circular RNA annexin A2 as a potential biomarker and therapeutic target for acute myeloid leukaemia. Am J Transl Res 2020; 12:1683-1699. [PMID: 32509169 PMCID: PMC7270033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 04/02/2020] [Indexed: 06/11/2023]
Abstract
This study was to investigate the circular RNA (circRNA) expression profile and the potential circRNAs as biomarkers and therapeutic targets for acute myeloid leukaemia (AML). CircRNA expression profile in bone marrow mononuclear cells from 5 AML patients and 5 healthy donor controls (HCs) was evaluated by microarray. Then, 10 candidate circRNAs (top 5 upregulated and top 5 downregulated) from microarray were validated by RT-qPCR in 130 AML patients and 50 HCs. Finally, the effects of circRNA annexin A2 (circ-ANXA2) knockdown on cell proliferation, apoptosis, chemosensitivity to cytarabine, daunorbicin and potential target microRNAs were assessed in THP-1 and KG-1 cells. By microarray, 173 upregulated and 181 downregulated circRNAs were found in AML patients than HCs, and these circRNAs were found in AML patients compared with HCs, and these circRNAs were implicated in AML-related pathways such as ErbB and EGFR pathways. By RT-qPCR, 9 of 10 candidate circRNAs (including circ-RPS6KB1, circ-CSMD2, circ-PTK2, circ-ANXA2, circ-PWP2, circ-RBM5, circ-ZZEF1, circ-GSK3B and circ-FOXP1) were dysregulated in AML patients compared with HCs. Circ-ANXA2 correlated with higher disease risk, poor risk stratification, lower complete remission level, shorter event-free survival and overall survival in AML. In cellular experiments, circ-ANXA2 was upregulated in AML cell lines, and its knockdown suppressed proliferation, enhanced apoptosis of THP-1 and KG-1 cells and increased their chemosensitivity to cytarabine and daunorbicin. Additionally, circ-ANXA2 knockdown promoted microRNA (miR)-23a-5p and miR-503-3p expression in THP-1 and KG-1 cells. In conclusion, our findings provide a macroscopic view of the circRNA expression profile in AML, and demonstrate that circ-ANXA2 may be a potential biomarker and therapeutic target for AML.
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Affiliation(s)
- Yi Ding
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Yan Dong
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Huina Lu
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Xiu Luo
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Jianfei Fu
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Bing Xiu
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Aibin Liang
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
| | - Wenjun Zhang
- Department of Hematology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, P.R. China
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Yang CM, Qiao GL, Song LN, Bao S, Ma LJ. Circular RNAs in gastric cancer: Biomarkers for early diagnosis. Oncol Lett 2020; 20:465-473. [PMID: 32565971 PMCID: PMC7285985 DOI: 10.3892/ol.2020.11623] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 04/09/2020] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs) are highly conserved and stable closed-loop non-coding RNAs. They are involved in numerous biological functions, including regulating gene transcription or protein translation by interacting with proteins and regulating expression of microRNAs. The aberrant expression of circRNAs has been reported in many cancers, including gastric cancer. By regulating gene expression, circRNAs are able to affect the proliferation, invasion and metastasis of gastric cancer. The current review focused on the characteristics and biological functions of circRNAs, the carcinogenic potential and the possible implications of circRNAs on the diagnosis and treatment of gastric cancer. In conclusion, circRNAs may serve as potential biomarkers for diagnosis, as well as therapeutic targets.
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Affiliation(s)
- Chun-Mei Yang
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.,Department of Clinical Laboratory Diagnostics, Beihua University, Jilin City, Jilin 132012, P.R. China
| | - Guang-Lei Qiao
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
| | - Li-Na Song
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
| | - Shisan Bao
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.,Discipline of Pathology, School of Medical Science and Bosch Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
| | - Li-Jun Ma
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
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Lin S, Song S, Sun R, Zhang M, Du Y, Zhang D, Xu W, Wang H. Oncogenic circular RNA Hsa‐circ‐000684 interacts with microRNA‐186 to upregulate ZEB1 in gastric cancer. FASEB J 2020; 34:8187-8203. [PMID: 32388910 DOI: 10.1096/fj.201903246r] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/01/2020] [Accepted: 04/03/2020] [Indexed: 12/19/2022]
Affiliation(s)
- Sen Lin
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
| | - Suzhen Song
- Department of Internal Medicine Shandong University of Traditional Chinese Medicine Ji'nan P. R. China
| | - Rong Sun
- Central Laboratory The Second Hospital of Shandong University Ji'nan P. R. China
| | - Mingbao Zhang
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
| | - Yating Du
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
| | - Dongdong Zhang
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
| | - Weihua Xu
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
| | - Hongbo Wang
- Department of Digestive Disease The Second Hospital of Shandong University Ji'nan P. R. China
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Ren G, Zhao Q, Yan C, Xue Q, Zhang L. Circular RNA circZFR promotes tumorigenic capacity of lung cancer via CCND1. Transl Cancer Res 2020; 9:3303-3311. [PMID: 35117697 PMCID: PMC8797637 DOI: 10.21037/tcr.2020.04.24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 03/12/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND To explore the role of circular RNA (circRNA) circZFR in tumorigenic capacity of lung cancer (LC). METHODS Thirty primary LC tissues were used to detect circRNAs expression. CircZFR was silenced in two LC cell lines using lentivirus-mediated short hairpins RNAs. Quantitative real time PCR (qRT-PCR), northern blot and in situ hybridization (ISH) assay were used to measure the expression of circRNA. RESULTS CircRNA circZFR was highly expressed in LC tumors. CircZFR deficiency significantly abrogated clone formation. CircZFR depletion substantially decreased tumor growth compared to WT control cells. CircZFR overexpression was dramatically increased cell growth in LC cell lines. Consequently, circZFR overexpression substantially promoted tumor propagation. Consistently, circZFR deficiency significantly reduced the expression of CCND1 and major cell cycle genes in LC cell lines. In contrast, circZFR depletion did not alter the expression of ZFR. Consequently, circZFR deficiency dramatically decreased H3K4me3 levels on the CCND1 promoter at -1,100 to -900 bp segment of CCND1 promoter. CONCLUSIONS CircZFR was related with LC growth in vitro and in vivo and tumorigenic capacity of LC. The possible mechanism was to regulating expression of CCND1, indicating the circZFR/CCND1 signaling might be a promising therapeutic target for LC treatment.
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Affiliation(s)
- Guanjun Ren
- Department of Respiratory Medicine, Beijing Aerospace General Hospital, Beijing 100076, China
| | - Qiuhong Zhao
- Department of Respiratory Medicine, Beijing Aerospace General Hospital, Beijing 100076, China
| | - Chunliang Yan
- Department of Respiratory Medicine, Beijing Aerospace General Hospital, Beijing 100076, China
| | - Qishan Xue
- Department of Respiratory Medicine, Beijing Aerospace General Hospital, Beijing 100076, China
| | - Li Zhang
- Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W. CircRNA: a rising star in gastric cancer. Cell Mol Life Sci 2020; 77:1661-1680. [PMID: 31659415 PMCID: PMC11104848 DOI: 10.1007/s00018-019-03345-5] [Citation(s) in RCA: 274] [Impact Index Per Article: 54.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 10/08/2019] [Accepted: 10/14/2019] [Indexed: 01/17/2023]
Abstract
In recent years, a large number of circRNAs have been identified in mammalian cells with high-throughput sequencing technologies and bioinformatics. The aberrant expression of circRNAs has been reported in many human diseases including gastric cancer (GC). The number of GC-related circRNAs with validated biological functions and mechanisms of action is growing. CircRNAs are critically involved in GC cell proliferation, apoptosis, migration, and invasion. CircRNAs have been shown to function as regulators of parental gene transcription and alternative splicing and miRNA sponges. Moreover, circRNAs have been suggested to interact with proteins to regulate their expression level and activities. Several circRNAs have been identified to encode functional proteins. Due to their great abundance, high stability, tissue- and developmental-stage-specific expression patterns, and wide distribution in various body fluids and exosomes, circRNAs exhibit a great potential to be utilized as biomarkers for GC. Herein, we briefly summarize their biogenesis, properties and biological functions and discuss about the current research progress of circRNAs in GC with a focus on the potential application for GC diagnosis and therapy.
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Affiliation(s)
- Rong Li
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Jiajia Jiang
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
| | - Hui Shi
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Hui Qian
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Xu Zhang
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China.
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
| | - Wenrong Xu
- Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, China.
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
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Li Y, Fan H, Sun J, Ni M, Zhang L, Chen C, Hong X, Fang F, Zhang W, Ma P. Circular RNA expression profile of Alzheimer's disease and its clinical significance as biomarkers for the disease risk and progression. Int J Biochem Cell Biol 2020; 123:105747. [PMID: 32315771 DOI: 10.1016/j.biocel.2020.105747] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 04/01/2020] [Accepted: 04/13/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To investigate circular RNA (circRNA) expression profile via microarray, and further assess the potential of candidate circRNAs as biomarkers in Alzheimer's disease (AD). METHODS CircRNA expression profile in cerebrospinal fluid from 8 AD patients and 8 control (Ctrl) subjects was assessed by microarray. Subsequently, 10 candidate circRNAs from microarray were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in cerebrospinal fluid from 80 AD patients and 40 Ctrl subjects. RESULTS By microarray, 112 circRNAs were upregulated and 51 circRNAs were downregulated in AD patients compared with Ctrl subjects, and these circRNAs were enriched in AD related pathways such as neurotrophin signaling pathway, natural killer cell mediated cytotoxicity and cholinergic synapse. By RT-qPCR, circ-LPAR1, circ-AXL and circ-GPHN were increased, whereas circ-PCCA, circ-HAUS4, circ-KIF18B and circ-TTC39C were decreased in AD patients compared with Ctrl subjects, and these circRNAs were disclosed to predict AD risk by receiver operating characteristics curve analysis. Further forward-stepwise multivariate logistic regression revealed that circ-AXL, circ-GPHN, circ-ITPR3, circ-PCCA and cic-TTC39C were independent predictive factors for AD risk. Besides, in AD patients, circ-AXL and circ-GPHN negatively correlated, while circ-PCCA and circ-HAUS4 positively correlated with mini-mental state examination score; Circ-AXL negatively correlated, while circ-PCCA, circ-HAUS4 and circ-KIF18B positively correlated with Aβ42; Circ-AXL and circ-GPHN positively correlated, whereas circ-HAUS4 negatively correlated with t-tau; Circ-AXL positively correlated with p-tau. CONCLUSION Our study provides an overview of circRNA expression profile in AD, and identifies that circ-AXL, circ-GPHN and circ-PCCA hold clinical implications for guiding disease management in AD patients.
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Affiliation(s)
- Yuanlong Li
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Hua Fan
- The First Affiliated Hospital of Henan University of Science and Technology, School of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
| | - Jun Sun
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Ming Ni
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Clinical Pharmacy, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
| | - Lei Zhang
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Ci Chen
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Xuejiao Hong
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Fengqin Fang
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Wei Zhang
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Peizhi Ma
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China.
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Li S, Teng S, Xu J, Su G, Zhang Y, Zhao J, Zhang S, Wang H, Qin W, Lu ZJ, Guo Y, Zhu Q, Wang D. Microarray is an efficient tool for circRNA profiling. Brief Bioinform 2020; 20:1420-1433. [PMID: 29415187 DOI: 10.1093/bib/bby006] [Citation(s) in RCA: 150] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 12/29/2017] [Indexed: 12/17/2022] Open
Abstract
Circular RNAs (circRNAs) are emerging as a new class of endogenous and regulatory noncoding RNAs in latest years. With the widespread application of RNA sequencing (RNA-seq) technology and bioinformatics prediction, large numbers of circRNAs have been identified. However, at present, we lack a comprehensive characterization of all these circRNAs in interested samples. In this study, we integrated 87 935 circRNAs sequences that cover most of circRNAs identified till now represented in circBase to design microarray probes targeting back-splice site of each circRNA to profile expression of those circRNAs. By comparing the circRNA detection efficiency of RNA-seq with this circRNA microarray, we revealed that microarray is more efficient than RNA-seq for circRNA profiling. Then, we found ∼80 000 circRNAs were expressed in cervical tumors and matched normal tissues, and ∼25 000 of them were differently expressed. Notably, many of these circRNAs detected by this microarray can be validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or RNA-seq. Strikingly, as many as ∼18 000 circRNAs could be robustly detected in cell-free plasma samples, and the expression of ∼2700 of them differed after surgery for tumor removal. Our findings provided a comprehensive and genome-wide characterization of circRNAs in paired normal tissues and tumors and plasma samples from multiple individuals. In addition, we also provide a rich resource with 41 microarray data sets and 10 RNA-seq data sets and strong evidences for circRNA expression in cervical cancer. In conclusion, circRNAs could be efficiently profiled by circRNA microarray to target their reported back-splice sites in interested samples.
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Guan E, Xu X, Xue F. circ-NOTCH1 acts as a sponge of miR-637 and affects the expression of its target gene Apelin to regulate gastric cancer cell growth. Biochem Cell Biol 2020; 98:164-170. [PMID: 31276627 DOI: 10.1139/bcb-2019-0079] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer (GC) is a major cause of cancer-related deaths worldwide, and has a low survival rate, low cure rate, high recurrence rate, and poor prognosis. Recent studies have indicated that circular RNAs (circRNAs) have important functions in the occurrence and progression of GC. Studies on circ-NOTCH1, which was shown to be highly expressed in GC, have indicated that miR-637 binds to circ-NOTCH1 at multiple sites, and a dual-luciferase reporter gene assay further confirmed that miR-637 indeed targeted circ-NOTCH1 and Apelin. Circ-NOTCH1 and Apelin are highly expressed in GC cells and tissues, whereas the expression of miR-637 is reduced. Circ-NOTCH1 and miR-637 do not regulate each other’s expression levels, but circ-NOTCH1significantly upregulates the expression of the miR-637 target gene Apelin, whereas miR-637 inhibites the expression of Apelin. Examination of GC cells showed that circ-NOTCH1 enhances cell proliferation and invasiveness, and reduces cell apoptosis; these effects were reversed by miR-637, which could terminate the above effects of circ-NOTCH1. When co-transfected with the circ-NOTCH1 overexpression plasmid and Apelin siRNAs, there were no obvious changes to the levels of cell proliferation, apoptosis, or invasiveness. Therefore, in GC cells, circ-NOTCH1 inhibits the transcriptional activity of miR-637, thereby upregulating the expression of its target gene Apelin and regulating cell proliferation, apoptosis, and invasiveness. This finding provides more experimental evidence for the function of circRNA in GC.
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Affiliation(s)
- Encui Guan
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
| | - Xiaoguang Xu
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
| | - Fangxi Xue
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
- Department of Gastroenterology, Linyi Central Hospital, 7# Health Road, Yishui County, Linyi 276400, Shandong Province, Linyi 276400, China
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The Regulatory Functions of Circular RNAs in Digestive System Cancers. Cancers (Basel) 2020; 12:cancers12030770. [PMID: 32213977 PMCID: PMC7140005 DOI: 10.3390/cancers12030770] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/19/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023] Open
Abstract
Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.
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Wang N, Lu K, Qu H, Wang H, Chen Y, Shan T, Ge X, Wei Y, Zhou P, Xia J. CircRBM33 regulates IL-6 to promote gastric cancer progression through targeting miR-149. Biomed Pharmacother 2020; 125:109876. [PMID: 32044717 DOI: 10.1016/j.biopha.2020.109876] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/16/2022] Open
Abstract
There is increasing evidence of the vital role played by circular RNAs (circRNAs) in the progression of gastric cancer (GC). A circRNA, hsa_circ_0001772, was generated from the RBM33 gene and named circRBM33. The aim of this study was to investigate the role of circRBM33 in GC. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of circRBM33 in 79 pairs of GC tissues and paracancerous tissues and 4 GC cell lines (MGC-803, BGC-823, SGC-7901, and AGS). Bioinformatics databases were used to predict downstream targets of circRNA and micro RNA (miRNA). Dual luciferase reporter assay was used to verify whether miR-149 was a direct binding target for circRBM33. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2´-deoxyuridine (EDU) assay, transwell assay, and flow-cytometric analyses were performed to determine the role of circRBM33 in the biological functioning of GC cells. Western blot technique was used to quantify the levels of interleukin-6 (IL-6). CircRBM33 was distinctly upregulated in GC specimens and cell lines and a close correlation between circRBM33 expression and clinical characteristics of GC was observed. After silencing circRBM33, the apoptosis of GC cells increased, while proliferation, migration, and invasion decreased. Rescue experiments indicated that circRBM33 manipulates biological function in GC cells through the circRBM33/miR-149/IL-6 axis. CircRBM33 can be used as a tumor biomarker and a possible therapeutic target in the future.
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Affiliation(s)
- Ning Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Keyu Lu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Huiheng Qu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Hao Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Yigang Chen
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Ting Shan
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Xuhui Ge
- Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yunyu Wei
- Department of Laboratory, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Peng Zhou
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Jiazeng Xia
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China.
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Naeli P, Pourhanifeh MH, Karimzadeh MR, Shabaninejad Z, Movahedpour A, Tarrahimofrad H, Mirzaei HR, Bafrani HH, Savardashtaki A, Mirzaei H, Hamblin MR. Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role. Crit Rev Oncol Hematol 2020; 145:102854. [PMID: 31877535 PMCID: PMC6982584 DOI: 10.1016/j.critrevonc.2019.102854] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 11/28/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called "back-splicing" from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as "microRNA sponge" and "RNA binding protein sponge" have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer.
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Affiliation(s)
- Parisa Naeli
- Department of Biological Sciences, Faculty of Genetics, Tarbiat Modares University, Tehran, Iran.
| | | | - Mohammad Reza Karimzadeh
- Department of Medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, School of Basic Sciences, TarbiatModares University, Tehran, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hossein Tarrahimofrad
- Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hassan Hassani Bafrani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Amir Savardashtaki
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences Shiraz, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.
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Zhang Y, Han T, Li J, Cai H, Xu J, Chen L, Zhan X. Comprehensive analysis of the regulatory network of differentially expressed mRNAs, lncRNAs and circRNAs in gastric cancer. Biomed Pharmacother 2019; 122:109686. [PMID: 31786464 DOI: 10.1016/j.biopha.2019.109686] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 11/10/2019] [Accepted: 11/16/2019] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer (GC) is one of the most common types of human cancers. However, the mechanisms underlying GC remained largely unclear. To determine whether the differentially expressed mRNAs, lncRNAs and circRNAs in GC, we screened conducted SBC-ceRNA microarray analysis in 3 pairs of GC and normal tissues. Furthermore, differentially expressed mRNAs mediated protein protein interaction (PPI) networks, lncRNAs mediated cis-regulatory network, and circRNA mediated ceRNA network were for the first time constructed to reveal their potential functions and mechanisms in GC. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was conducted to validate the microarray analysis. A total of 922 mRNAs, 2112 lncRNAs and 2896 circRNAs were observed to be dysregulated in GC samples. Bioinformatics analysis showed these differentially expressed genes (DEGs) were significantly associated with regulating branched - chain amino acid catabolic process, Glycolysis/Gluconeogenesis and ARF protein signal transduction. Moreover, we found the dysregulation of key mRNAs and lncRNAs were associated with the overall survival time in GC patients. We believe this study provides useful information for understanding the mechanism underlying GC progression and exploring potential therapeutic and prognostic targets for GC.
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Affiliation(s)
- Yingyi Zhang
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China
| | - Ting Han
- Department of General Surgery, Changhai Hospital, Second Military Medical University, 200433, China
| | - Jie Li
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China
| | - Hui Cai
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China
| | - Jing Xu
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China
| | - Longpei Chen
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China
| | - Xianbao Zhan
- Department of Oncology, Changhai Hospital, Second Military Medical University, 200433, China.
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42
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Cao C, Han S, Yuan Y, Wu Y, Lian W, Zhang X, Pan L, Li M. Downregulated Circular RNA hsa_circ_0000291 Suppresses Migration And Proliferation Of Gastric Cancer Via Targeting The miR-183/ITGB1 Axis. Cancer Manag Res 2019; 11:9675-9683. [PMID: 31814763 PMCID: PMC6862805 DOI: 10.2147/cmar.s213830] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 09/28/2019] [Indexed: 12/18/2022] Open
Abstract
Background Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported. Objective To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion. Materials and methods In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation. Results Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 “sponging,” which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype. Conclusion Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.
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Affiliation(s)
- Chuanwu Cao
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Shilong Han
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Yifeng Yuan
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Yongfa Wu
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Weishuai Lian
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Xiaojun Zhang
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Long Pan
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
| | - Maoquan Li
- Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China
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43
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Wang F, Li X, Zhao X, Xue Y. Detection of a 5-circRNA signature to improve prognostic prediction in gastric cancer. J Investig Med 2019; 68:762-769. [PMID: 31672718 DOI: 10.1136/jim-2019-001131] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2019] [Indexed: 01/10/2023]
Abstract
Gastric cancer (GC) is a commonly diagnosed malignancy with a high mortality rate worldwide. Despite advances in therapeutic approaches, the 5-year survival rate of patients with GC remains poor. A type of non-coding RNA, circular RNA (circRNA), has been discovered. Some circRNAs are dysregulated in cancer and may have important functions. Thus, circRNAs could be candidate biomarkers for disease diagnosis and prognosis. Our study used a reannotation framework to derive expression values of circRNAs from microarray data sets. We used an integrated pipeline including differential expression analysis and Cox regression analyses to detect GC-associated circRNA signatures. We validated results with 54 paired gastric tumor and adjacent normal tissues. Five circRNA signatures were highly associated with patient overall survival and disease-free survival. Real-time PCR experiments on hsa_circ_0103398 and hsa_circ_0127859 in tumors and normal tissues showed that these circRNAs were significantly upregulated in GC. High expression of hsa_circ_0103398 and hsa_circ_0127859 was closely associated with unfavorable survival time. Our findings indicated that a 5-circRNA signature might serve as a candidate prognostic biomarker of GC.
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Affiliation(s)
- Fengjiao Wang
- Department of Thoracic Surgery, Cancer Hospital, Harbin Medical University, Harbin, China
| | - Xuexin Li
- Department of Urinary Surgery, Cancer Hospital, Harbin Medical University, Harbin, China
| | - Xingkai Zhao
- The First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Cancer Hospital, Harbin Medical University, Harbin, China
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44
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Fang X, Wen J, Sun M, Yuan Y, Xu Q. CircRNAs and its relationship with gastric cancer. J Cancer 2019; 10:6105-6113. [PMID: 31762820 PMCID: PMC6856571 DOI: 10.7150/jca.32927] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 08/18/2019] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs), as a type of tissue specific RNA with more stable structure than linear RNAs, was poorly understood on its correlation with gastric cancer (GC). In this review, we outline the synthesis and characteristics of circRNAs and generalize their categories and functions. Through comprehensive analysis of the reported results, we find that circRNAs not only participate in the regulation of gastric cancer (GC) cell biological behaviors, such as proliferation, invasion, migration and epithelial mesenchymal transition (EMT), but also are related to the clinicopathological features of GC such as tumor differentiation, TNM stage and metastasis, etc. According to the present screening and verification results, circRNAs are suggested to be used as biomarkers for the early diagnosis and prognosis prediction of GC, and those circRNAs involved in the genesis and development of GC have the potential as novel targets for the individualized treatment of GC.
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Affiliation(s)
- Xinxin Fang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Jing Wen
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
| | - Mingjun Sun
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Key Laboratory of Gastrointestinal Cancer Etiology and Screening, Liaoning Province, Shenyang 110001, China
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45
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Shan C, Zhang Y, Hao X, Gao J, Chen X, Wang K. Biogenesis, functions and clinical significance of circRNAs in gastric cancer. Mol Cancer 2019; 18:136. [PMID: 31519189 PMCID: PMC6743094 DOI: 10.1186/s12943-019-1069-0] [Citation(s) in RCA: 172] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/06/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.
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Affiliation(s)
- Chan Shan
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
| | - Yinfeng Zhang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Xiaodan Hao
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Jinning Gao
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Xinzhe Chen
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Kun Wang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
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46
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Jiang F, Shen X. Current prevalence status of gastric cancer and recent studies on the roles of circular RNAs and methods used to investigate circular RNAs. Cell Mol Biol Lett 2019; 24:53. [PMID: 31428168 PMCID: PMC6698018 DOI: 10.1186/s11658-019-0178-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 07/31/2019] [Indexed: 12/29/2022] Open
Abstract
Gastric cancer is a malignant tumor with the fifth incidence and third mortality worldwide. There were 951,000 new cases and about 723,000 patients died of it in 2012. Undoubtedly, gastric cancer has been affecting people's living standards, and is already a major public health problem in China with its population growth and ageing. Even though the detection methods and medical standards have improved, the five-year survival rate of people is still very low. While circular RNA (circRNA) is increasingly attracting attention from researchers, at the same time, its mystery has gradually been uncovered. Many studies have shown that circRNA can act as molecular sponge of miRNA to regulate gene expression and has an obviously different expression profile between cancerous and normal groups, which arouse people's curiosity and provide new opportunities for early detection of gastric cancer to improve the quality of life of patients. This study reviews current prevalence of gastric cancer in the word and China, as well as the characteristics and functions of circRNA and common laboratory detection methods involving circRNA in gastric cancer.
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Affiliation(s)
- Fei Jiang
- Key Laboratory of Environmental Medical Engineering and Education Ministry, Nanjing Public Health College, Southeast University, Nanjing, 210000 China
- Department of Preventive Medicine, Nanjing Public Health College, Southeast University, Nanjing, 210000 China
| | - Xiaobing Shen
- Key Laboratory of Environmental Medical Engineering and Education Ministry, Nanjing Public Health College, Southeast University, Nanjing, 210000 China
- Department of Preventive Medicine, Nanjing Public Health College, Southeast University, Nanjing, 210000 China
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47
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Chen Z, Ju H, Zhao T, Yu S, Li P, Jia J, Li N, Jing X, Tan B, Li Y. hsa_circ_0092306 Targeting miR-197-3p Promotes Gastric Cancer Development by Regulating PRKCB in MKN-45 Cells. MOLECULAR THERAPY-NUCLEIC ACIDS 2019; 18:617-626. [PMID: 31689616 PMCID: PMC6838893 DOI: 10.1016/j.omtn.2019.08.012] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 07/11/2019] [Accepted: 08/07/2019] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is one of the most common cancers worldwide and is thus a global cancer burden. Here, we focused on a novel circular RNA hsa_circ_0092306 and explored the potential molecular mechanism to provide a new target for and novel insights into GC treatment. The GEO microarray was mined and analyzed with R software. Sanger sequencing and RNase R assay were applied to verify the identification of hsa_circ_0092306. Quantitative real-time PCR and western blot were performed to measure the mRNA and protein levels. Pull-down and luciferase reporter assays were conducted to confirm the target relationships. Annexin V-PI apoptosis flow cytometry, 3-(4,5Dimethylthiazol- yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays were applied to detect cell apoptosis, viability, migration, and invasion in MKN-45 cells, respectively. A xenograft in vivo experiment was conducted to confirm the cell experiment results. hsa_circ_0092306 was upregulated in GC tissues and GC cells, and promoted GC development in MKN-45 cells. hsa_circ_0092306 inhibited tumor suppressor miR-197-3p expression but promoted tumor promotor protein kinase C beta (PRKCB) expression in MKN-45 cells. hsa_circ_0092306 and PRKCB had a common target (miR-197-3p) and were negatively related to miR-197-3p expression. hsa_circ_0092306 promoted the development of GC by regulating the pathway of miR-197-3p/PRKCB in MKN-45 cells.
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Affiliation(s)
- Zihao Chen
- Graduate School of Hebei Medical University, Shijiazhuang 050017, Hebei, China; The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
| | - Hongping Ju
- School of Medicine, Kunming University, Kunming 650214, Yunnan, China; The Respiratory System Disease Prevention and Control of Public Service Platform of Science and Technology in Yunnan Province, Kunming 650214, Yunnan, China.
| | - Ting Zhao
- Graduate School of Hebei Medical University, Shijiazhuang 050017, Hebei, China
| | - Shan Yu
- School of Medicine, Kunming University, Kunming 650214, Yunnan, China
| | - Ping Li
- School of Medicine, Kunming University, Kunming 650214, Yunnan, China
| | - Jing Jia
- School of Medicine, Kunming University, Kunming 650214, Yunnan, China
| | - Nan Li
- School of Medicine, Kunming University, Kunming 650214, Yunnan, China
| | - Xiaojie Jing
- Department of Medicine, The People's Hospital of Economic and Technological Development Zone, Kunming 650217, Yunnan, China
| | - Bibo Tan
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
| | - Yong Li
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China.
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48
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Predicting human disease-associated circRNAs based on locality-constrained linear coding. Genomics 2019; 112:1335-1342. [PMID: 31394170 DOI: 10.1016/j.ygeno.2019.08.001] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/01/2019] [Accepted: 08/02/2019] [Indexed: 12/12/2022]
Abstract
Circular RNAs (circRNAs) are a new kind of endogenous non-coding RNAs, which have been discovered continuously. More and more studies have shown that circRNAs are related to the occurrence and development of human diseases. Identification of circRNAs associated with diseases can contribute to understand the pathogenesis, diagnosis and treatment of diseases. However, experimental methods of circRNA prediction remain expensive and time-consuming. Therefore, it is urgent to propose novel computational methods for the prediction of circRNA-disease associations. In this study, we develop a computational method called LLCDC that integrates the known circRNA-disease associations, circRNA semantic similarity network, disease semantic similarity network, reconstructed circRNA similarity network, and reconstructed disease similarity network to predict circRNAs related to human diseases. Specifically, the reconstructed similarity networks are obtained by using Locality-Constrained Linear Coding (LLC) on the known association matrix, cosine similarities of circRNAs and diseases. Then, the label propagation method is applied to the similarity networks, and four relevant score matrices are respectively obtained. Finally, we use 5-fold cross validation (5-fold CV) to evaluate the performance of LLCDC, and the AUC value of the method is 0.9177, indicating that our method performs better than the other three methods. In addition, case studies on gastric cancer, breast cancer and papillary thyroid carcinoma further verify the reliability of our method in predicting disease-associated circRNAs.
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49
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Shen YQ, Pan JJ, Sun ZY, Chen XQ, Zhou XG, Zhou XY, Cheng R, Yang Y. Differential expression of circRNAs during rat lung development. Int J Mol Med 2019; 44:1399-1413. [PMID: 31432143 PMCID: PMC6713411 DOI: 10.3892/ijmm.2019.4299] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 06/28/2019] [Indexed: 12/14/2022] Open
Abstract
At present, thousands of circular RNAs (circRNAs) have been found in cancer and various tissues from different species. However, the expression of circRNAs during rat lung development remains largely unknown. In the present study, circRNA expression profiles were screened in three mixed rat lung tissues at 3 time-points [embryonic day (E) 19, E21 and post-natal (P) day 3] during fetal rat development with circRNA high-throughput sequencing. Preliminary results were verified by reverse transcription-PCR (RT-PCR) at 4 time-points (E16, E19, E21 and P3). A total of 375 circRNAs were differently expressed in E19 vs. E21 (fold change ≥1.5; P<0.05). At the same time, a total of 358 circRNAs were differently expressed in E21 vs. P3 (fold change ≥1.5; P<0.05). A total of 3 circRNAs (rno_circ:chr7:24777879-24784993, r n o _c i r c:c h r14:14 62 0 910 −14 62 49 33 a n d r n o _circ:chr3:1988750- 1998592) were characterized by having consistent fold changes (≥1.5) between 3 time-points (E19, E21 and P3) and were selected for RT-PCR at 4 time-points (E16, E19, E21 and P3). Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of parent genes of the differentially expressed circRNAs revealed that these circRNAs may serve important roles in lung development. The present results support that these new found circRNAs participate in lung development. Furthermore, these findings may help to clarify the physiopathological mechanism of normal rat lung development, and may further provide a physiopatho-logical basis of lung developmental diseases.
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Affiliation(s)
- Yan-Qing Shen
- Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - Jing-Jing Pan
- Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Zhong-Yi Sun
- Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xiao-Qing Chen
- Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xiao-Guang Zhou
- Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - Xiao-Yu Zhou
- Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - Rui Cheng
- Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - Yang Yang
- Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
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Chen LH, Wang LP, Ma XQ. Circ_SPECC1 enhances the inhibition of miR-526b on downstream KDM4A/YAP1 pathway to regulate the growth and invasion of gastric cancer cells. Biochem Biophys Res Commun 2019; 517:253-259. [PMID: 31349968 DOI: 10.1016/j.bbrc.2019.07.065] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 07/18/2019] [Indexed: 01/24/2023]
Abstract
Gastric cancer (GC) is a common malignant tumor, and many studies have shown that circular RNAs (circRNAs) play important roles in the progress of GC. This study showed that circ_SPECC1 was down-regulated in various GC cell lines, significantly inhibited GC cell proliferation and invasion, and promote apoptosis, which might play an anti-oncogene role. Circ_SPECC1 was mainly located in the cytoplasm, and its sequence contained multiple potential binding sites of miR-526b. Pull-down experiments with biotinylated miR-526b mimics and circ_SPECC1 probe showed that they could enrich each other. RIP experiments found hat anti-AGO2 antibody could significantly enrich circ_SPECC1. Further dual luciferase reporter gene assay also confirmed that miR-526b could bind directly to circ_SPECC1. miR-526b was also down-regulated in GC cells, and one of its important target genes was KDM4A. Both circ_SPECC1 and miR-526b inhibited the expression of KDM4A and its downstream effector YAP1, but miR-526b inhibitors terminated the above-mentioned inhibition of circ_SPECC1, and KDM4A overexpression reversed the inhibition of circ_SPECC1 and miR-526b on YAP1 expression. Both miR-526b and KDM4A siRNA inhibited GC cell proliferation and invasion, and promote apoptosis; KDM4A overexpression had the opposite effects, and significantly blocked the regulation of miR-526b on cell growth and invasion. Therefore, circ_SPECC1 can enhance miR-526b inhibitory effect on downstream KDM4A/YAP1 pathway by adsorbing it, thus inhibiting GC cell growth and invasion. These findings enrich the mechanism of circRNAs in GC and will provide more new targets for the prevention and treatment of GC.
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Affiliation(s)
- Li-Hua Chen
- Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
| | - Lin-Pei Wang
- Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
| | - Xiao-Qiu Ma
- Department of Internal Medical Oncology, The 910th Hospital of the People's Liberation Army, Quanzhou, 362000, Fujian, China.
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