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Jahantab MB, Salehi M, Koushki M, Farrokhi Yekta R, Amiri-Dashatan N, Rezaei-Tavirani M. Modelling of miRNA-mRNA Network to Identify Gene Signatures with Diagnostic and Prognostic Value in Gastric Cancer: Evidence from In-Silico and In-Vitro Studies. Rep Biochem Mol Biol 2024; 13:281-300. [PMID: 39995653 PMCID: PMC11847593 DOI: 10.61186/rbmb.13.2.281] [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: 07/09/2024] [Accepted: 12/08/2024] [Indexed: 02/26/2025]
Abstract
Background Gastric cancer (GC) is a prevalent malignancy with high recurrence. Advances in systems biology have identified molecular pathways and biomarkers. This study focuses on discovering gene and miRNA biomarkers for diagnosing and predicting survival in GC patients. Methods Three sets of genes (GSE19826, GSE81948, and GSE112369) and two sets of miRNA expression (GSE26595, GSE78775) were obtained from the Gene Expression Omnibus (GEO), and subsequently, differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Functional pathway enrichment, DEG-miR-TF-protein-protein interaction network, DEM-mRNA network, ROC curve, and survival analyses were performed. Finally, qRT-PCR was applied to validate our results. Results From the high-throughput profiling studies of GC, we investigated 10 candidate mRNA and 7 candidate miRNAs as potential biomarkers. Expression analysis of these hubs revealed that 5 miRNAs (including miR-141-3p, miR-204-5p, miR-338-3p, miR-609, and miR-369-5p) were significantly upregulated compared to the controls. The genes with the highest degree included 6 upregulated and 4 downregulated genes in tumor samples compared to controls. The expression of miR-141-3p, miR-204-5p, SESTD1, and ANTXR1 were verified in vitro from these hub DEMs and DEGs. The findings indicated a decrease in the expression of miR-141-3p and miR-204-5p and increased expression of SESTD1 and ANTXR1 in GC cell lines compared to the GES-1 cell line. Conclusions The current investigation successfully recognized a set of prospective miRNAs and genes that may serve as potential biomarkers for GC's early diagnosis and prognosis.
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Affiliation(s)
- Mohammad Bagher Jahantab
- Clinical Research Development Unit, Shahid Jalil Hospital, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Mohammad Salehi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Mehdi Koushki
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Reyhaneh Farrokhi Yekta
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nasrin Amiri-Dashatan
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Yan S, Wang Z, Lan D, Niu J, Jian X, He F, Tang W, Hu C, Liu W. Circ_PABPC1 promotes the malignancy of gastric cancer through interacting with ILK to activate NF-κB pathway. Exp Cell Res 2024; 438:114058. [PMID: 38688434 DOI: 10.1016/j.yexcr.2024.114058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 04/22/2024] [Accepted: 04/24/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Gastric cancer (GC) is a common cancer type with both high incidence and mortality. Recent studies have revealed an important role of circRNA in the development of GC. However, more experiments are needed to reveal the precise molecular mechanisms of circRNA in GC development. METHODS Bioinformatics analysis was conducted to predict the potential role of circ_PABPC1 in GC and the target proteins of circ_PABPC1. Quantitative RT-PCR, Western blot and immunohistochemistry assays were conducted to detect the levels of circ_PABPC1, NF-κB p65, NF-κB p65 (Ser536) and ILK. MTT, Edu staining, cell scratch-wound and trans-well assays were carried out to detect cell proliferation, migration and invasion. The interaction between ILK and circ_PABPC1 was confirmed by RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization assays. Genetically modified GC cells were injected into mice to evaluate the tumor growth performance. RESULTS This study found that the high expression of circ_PABPC1 was associated with a poor prognosis of GC. The up-regulation of circ_PABPC1 promoted the proliferation, migration and invasion of GC cells. Circ_PABPC1 bound to ILK protein, thereby preventing the degradation of ILK. ILK mediated the effect of circ_PABPC1 on GC cells through activating NF-κB. CONCLUSION circ_PABPC1 promotes the malignancy of GC cells through binding to ILK to activate NF-κB signaling pathway.
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Affiliation(s)
- Siqi Yan
- Departments of Oncology, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, 410011, China; Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Zhu Wang
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Dongqiang Lan
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Junjie Niu
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Xiaolan Jian
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Fengjiao He
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China; Departments of Oncology, Xiangya Hospital of Central-South University, Changsha, Hunan, 410008, China
| | - Weizhi Tang
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China
| | - Chunhong Hu
- Departments of Oncology, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, 410011, China.
| | - Wei Liu
- Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China.
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Li R, Wang J, Xie Z, Tian X, Hou J, Wang D, Qian H, Shen H, Xu W. CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin. Oncogene 2024; 43:1033-1049. [PMID: 38366146 PMCID: PMC10978489 DOI: 10.1038/s41388-024-02968-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 02/01/2024] [Accepted: 02/05/2024] [Indexed: 02/18/2024]
Abstract
Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting β-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.
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Affiliation(s)
- Rong Li
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Junyi Wang
- Centre of Clinical Laboratory, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, China
| | - Zhenfan Xie
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Xinyu Tian
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Jie Hou
- Department of Clinical Laboratory, People's Hospital of Yangzhong City, 235 Yangzi Middle Road, Zhenjiang, Jiangsu, 212200, China
| | - Dongli Wang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Han Shen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
| | - Wenrong Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
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Kreissner KO, Faller B, Talucci I, Maric HM. MARTin-an open-source platform for microarray analysis. FRONTIERS IN BIOINFORMATICS 2024; 4:1329062. [PMID: 38405547 PMCID: PMC10885354 DOI: 10.3389/fbinf.2024.1329062] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 01/15/2024] [Indexed: 02/27/2024] Open
Abstract
Background: Microarray technology has brought significant advancements to high-throughput analysis, particularly in the comprehensive study of biomolecular interactions involving proteins, peptides, and antibodies, as well as in the fields of gene expression and genotyping. With the ever-increasing volume and intricacy of microarray data, an accurate, reliable and reproducible analysis is essential. Furthermore, there is a high level of variation in the format of microarrays. This not only holds true between different sample types but is also due to differences in the hardware used during the production of the arrays, as well as the personal preferences of the individual users. Therefore, there is a need for transparent, broadly applicable and user-friendly image quantification techniques to extract meaningful information from these complex datasets, while also addressing the challenges posed by specific microarray and imager formats, which can flaw analysis and interpretation. Results: Here we introduce MicroArray Rastering Tool (MARTin), as a versatile tool developed primarily for the analysis of protein and peptide microarrays. Our software provides state-of-the-art methodologies, offering researchers a comprehensive tool for microarray image quantification. MARTin is independent of the microarray platform used and supports various configurations including high-density formats and printed arrays with significant x and y offsets. This is made possible by granting the user the ability to freely customize parts of the application to their specific microarray format. Thanks to built-in features like adaptive filtering and autofit, measurements can be done very efficiently and are highly reproducible. Furthermore, our tool integrates metadata management and integrity check features, providing a straightforward quality control method, along with a ready-to-use interface for in-depth data analysis. This not only promotes good scientific practice in the field of microarray analysis but also enhances the ability to explore and examine the generated data. Conclusion: MARTin has been developed to empower its users with a reliable, efficient, and intuitive tool for peptidomic and proteomic array analysis, thereby facilitating data-driven discovery across disciplines. Our software is an open-source project freely available via the GNU Affero General Public License licence on GitHub.
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Affiliation(s)
- Kai O. Kreissner
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany
| | | | - Ivan Talucci
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany
- Department of Neurology, University Hospital Würzburg, Würzburg, Bavaria, Germany
| | - Hans M. Maric
- Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany
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Li S, Zeng Y, He L, Xie X. Exploring Prognostic Immune Microenvironment-Related Genes in Head and Neck Squamous Cell Carcinoma from the TCGA Database. J Cancer 2024; 15:632-644. [PMID: 38213736 PMCID: PMC10777048 DOI: 10.7150/jca.89581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/13/2023] [Indexed: 01/13/2024] Open
Abstract
Purpose: Head and neck squamous cell carcinoma (HNSCC) has a high rate of local and distant metastases. In tumor tissues, the interaction between tumor cells and the tumor microenvironment (TME) is closely related to cancer development and prognosis. Therefore, screening for TME-related genes in HNSCC is crucial for understanding metastatic patterns. Methods: Our research relied mainly on a novel algorithm called Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE). Fragments Per Kilobase of exon model per Million mapped fragments (FPKM) data and HNSCC clinical data were obtained from the TCGA database, and the purity of HNSCC tissue and the features of stromal and immune cell infiltration were determined. Furthermore, differentially expressed genes (DEGs) were screened based on immune, stromal, and ESTIMATE scores, and their protein-protein interaction (PPI) networks and ClueGO functions were evaluated. Finally, the expression profiles of DEGs related to immunity in HNSCC were determined. Differential gene expression was verified in the highly invasive oral cancer cell lines (SCC-25, CAL-27, and FaDu) and oral cancer tissues. Results: Our analysis found that both the immune and ESTIMATE scores were significantly associated with the prognosis of HNSCC. Moreover, cross-validation using the Venn algorithm revealed that 433 genes were significantly upregulated, and 394 genes were significantly downregulated. All DEGs were associated with both ESTIMATE and immune scores. The enrichment of cytokine-cytokine receptor interactions and chemokine signaling pathways was observed using pathway enrichment analyses. We initially screened 25 genes after analyzing the key sub-networks of the PPI network. Survival analysis revealed the significance of CCR4, CXCR3, P2RY14, CCR2, CCR8, and CCL19 in relation to survival and their association with immune infiltration-related metastasis in HNSCC. Conclusions: The expression profiles of relevant TME-related genes were screened following stromal and immune cell scoring using ESTIMATE, and DEGs associated with survival were identified. These TME-related gene markers offer valuable utility as both prognostic indicators and markers denoting metastatic traits in HNSCC.
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Affiliation(s)
- Shuangjiang Li
- Department of Stomatology, Changsha Stomatological Hospital, Changsha, P. R. China
| | - Yiyu Zeng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, P. R. China
| | - Liming He
- Department of Stomatology, Changsha Stomatological Hospital, Changsha, P. R. China
| | - Xiaoyan Xie
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, P. R. China
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Li M, Gao X, Miao T, Sun H. Identification of biomarkers of acne based on transcriptome analysis and combined with network pharmacology to explore the therapeutic mechanism of Jinhuang ointment. Medicine (Baltimore) 2023; 102:e35642. [PMID: 37933032 PMCID: PMC10627606 DOI: 10.1097/md.0000000000035642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 09/22/2023] [Indexed: 11/08/2023] Open
Abstract
The incidence of acne is on the rise due to unhealthy diet and living habits. Jinhuang ointment (JHO) is a classic prescription composed of 10 kinds of commonly used Chinese herbal medicine, which has been widely used in clinical prevention and treatment of skin inflammatory diseases since ancient times. However, the pharmacological mechanism and target of JHO are not clear. The acne microarray dataset was downloaded from gene expression omnibus database to identify differentially expressed genes (DEG). Immune infiltration was analyzed by CiberSort algorithm. HUB gene was identified by protein-protein interaction network. The gene expression omnibus dataset validates the biomarkers of acne with high diagnostic value. The potential active components and targets of JHO were obtained through Traditional Chinese Medicine Systems Pharmacology database, and the therapeutic targets were obtained by crossing with disease targets. R-packet is used for enrichment analysis. Molecular docking using Auto Dock Tools. A total of 202 DEGs were identified from 12 skin samples in the GSE6475. Immune infiltration analysis showed that there were a large number of macrophages and mast cells in acne skin. Gene set enrichment analysis analysis showed that DEGS was mainly involved in bacterial reaction, inflammatory reaction and so on. Six central genes and gene cluster modules were identified by Cytoscape software. A total of 185 JHO active components and 220 targets were obtained, of which 10 targets were potential targets for JHO in the treatment of acne. Kyoto encyclopedia of genes and genomes enrichment analysis showed that JHO treatment of acne was mainly related to Toll-like receptors, IL-17 and other signal pathways. The results of molecular docking showed that 5 active compounds in JHO had strong binding activity to the core protein receptor. IL-1 β, CXCL8, toll-like receptor 2, CXCL2, LCN2, and secretory phosphoprotein 1 may be potential biomarkers for early diagnosis of acne. JHO active components may regulate skin cell metabolism and inflammatory response and improve cellular immune microenvironment by acting on core targets (CXCL8, ESR1, IL-1 β, MMP1, MMP3, secretory phosphoprotein 1), thus achieving the purpose of treating acne. This is the result of the joint action of multiple targets and multiple pathways. It provides an idea for the development of a new combination of drugs for the treatment of acne.
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Affiliation(s)
- Minghui Li
- Shandong Women’s University, Jinan City, Shandong Province, China
| | - Xue Gao
- Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, China
| | - Tianai Miao
- Shandong Women’s University, Jinan City, Shandong Province, China
| | - Hongfeng Sun
- Shandong Women’s University, Jinan City, Shandong Province, China
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Chen H, Hu S, Yang R, Hu S, Yao Q, Zhao Y, Lian J, Ji A, Cao Y, Sun Q. The screening and validation process of miR-223-3p for saliva identification. Leg Med (Tokyo) 2023; 65:102312. [PMID: 37603982 DOI: 10.1016/j.legalmed.2023.102312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 07/25/2023] [Accepted: 08/03/2023] [Indexed: 08/23/2023]
Abstract
More accurate identification of the types of body fluids left at a crime scene is indispensable for improving the judicial chain of evidence. MicroRNAs (miRNAs) have become recognized as ideal molecular markers for the identification of body fluids in forensic science due to their short length, stability and high tissue specificity. In this study, small RNA sequencing was performed on 20 samples of five types of body fluids (peripheral blood, menstrual blood, saliva, semen, and vaginal secretions) with the BGISEQ-500 sequencing platform, and the specific miRNA markers of saliva and vaginal secretions were screened by bioinformatics methods, including differential expression analysis and significant enrichment analysis. Through RT-qPCR validation of 169 samples, we confirmed that miR-223-3p can be used as a saliva-specific marker. In addition, we considered miR-223-3p in combination with four other miRNA molecules (miR-451a, miR-891a-5p, miR-144-5p, miR-203a-3p) that had been previously screened and verified in our laboratory, and seven body fluid prediction models based on machine learning algorithms were constructed and verified. The results showed that a kernel density estimation (KDE) model based on the five miRNA markers for body fluid identification could achieve 100% accuracy in the samples tested in the present study.
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Affiliation(s)
- Huixiang Chen
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China; Faculty of Forensic Sciences, Shanxi Medical University, Taiyuan 030001, Shanxi, China
| | - Sheng Hu
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China
| | - Rui Yang
- Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Shuxiao Hu
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China; School of Investigation, People's Public Security University of China, Beijing 100038, China
| | - Qianwei Yao
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China; Faculty of Forensic Sciences, Shanxi Medical University, Taiyuan 030001, Shanxi, China
| | - Yixia Zhao
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China
| | - Jie Lian
- School of Investigation, People's Public Security University of China, Beijing 100038, China
| | - Anquan Ji
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China.
| | - Yang Cao
- Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.
| | - Qifan Sun
- MPS's Key Laboratory of Forensic Genetics, National Engineering Laboratory for Crime Scene Evidence Investigation and Examination, Institute of Forensic Science, Ministry of Public Security (MPS), Beijing 100038, China.
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Shao Z, Yuan C, Hu J, Wu Y, Zeng C. Circ_0003789 Facilitates Gastric Cancer Progression by Inducing the Epithelial-Mesenchymal Transition Through the Wnt/β-Catenin Signaling Pathway. Cancer Biother Radiopharm 2023; 38:102-110. [PMID: 32865426 DOI: 10.1089/cbr.2020.4044] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: The role of circular RNAs in the pathogenesis of gastric cancer (GC) has been well documented by numerous studies. However, whether circ_0003789 plays a role during GC progression remains to be determined. Thus, this study investigated the biological functions of circ_0003789 during GC progression. Materials and Methods: Circ_0003789 expression was determined using quantitative real-time polymerase chain reaction in GC and matched para-carcinoma normal tissues. Functional experiments were performed to estimate changes in the proliferation, apoptosis, migration, and invasion of GC cells treated to silence circ_0003789. E-cadherin, vimentin, Wnt3a, and β-catenin expression was determined using immunofluorescence staining and Western blot assays. Xenograft tumor growth and Ki67 expression were also evaluated in vivo. Results: Circ_0003789 was upregulated in GC tissues and cells, and its upregulation positively correlated with poor tumor differentiation, distal metastasis, and advanced clinical stage. Silencing circ_0003789 inhibited GC cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT), both in vitro and in vivo. Mechanistically, the Wnt/β-catenin signaling pathway was repressed by circ_0003789 silencing. Conclusions: Circ_0003789 facilitates GC progression by inducing the EMT through the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Zhongbao Shao
- Department of Electronic Information Engineering, Guangzhou College of Technology and Business, Guangzhou, China
| | - Chang Yuan
- Department of Electronic Information Engineering, Guangzhou College of Technology and Business, Guangzhou, China
| | - Junbao Hu
- Department of Electronic Information Engineering, Guangzhou College of Technology and Business, Guangzhou, China
| | - Yuli Wu
- Department of Electronic Information Engineering, Guangzhou College of Technology and Business, Guangzhou, China
| | - Chong Zeng
- Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, China
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Sharma U, Tuli HS, Uttam V, Choudhary R, Sharma B, Sharma U, Prakash H, Jain A. Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs. Pharmacol Res 2022; 186:106523. [DOI: 10.1016/j.phrs.2022.106523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 11/13/2022]
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Li XY, Wang SL, Chen DH, Liu H, You JX, Su LX, Yang XT. Construction and Validation of a m7G-Related Gene-Based Prognostic Model for Gastric Cancer. Front Oncol 2022; 12:861412. [PMID: 35847903 PMCID: PMC9281447 DOI: 10.3389/fonc.2022.861412] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 05/26/2022] [Indexed: 12/14/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. Chinese cases of GC account for about 40% of the global rate, with approximately 1.66 million people succumbing to the disease each year. Despite the progress made in the treatment of GC, most patients are diagnosed at an advanced stage due to the lack of obvious clinical symptoms in the early stages of GC, and their prognosis is still very poor. The m7G modification is one of the most common forms of base modification in post-transcriptional regulation, and it is widely distributed in the 5′ cap region of tRNA, rRNA, and eukaryotic mRNA. Methods RNA sequencing data of GC were downloaded from The Cancer Genome Atlas. The differentially expressed m7G-related genes in normal and tumour tissues were determined, and the expression and prognostic value of m7G-related genes were systematically analysed. We then built models using the selected m7G-related genes with the help of machine learning methods.The model was then validated for prognostic value by combining the receiver operating characteristic curve (ROC) and forest plots. The model was then validated on an external dataset. Finally, quantitative real-time PCR (qPCR) was performed to detect gene expression levels in clinical gastric cancer and paraneoplastic tissue. Results The model is able to determine the prognosis of GC samples quantitatively and accurately. The ROC analysis of model has an AUC of 0.761 and 0.714 for the 3-year overall survival (OS) in the training and validation sets, respectively. We determined a correlation between risk scores and immune cell infiltration and concluded that immune cell infiltration affects the prognosis of GC patients. NUDT10, METTL1, NUDT4, GEMIN5, EIF4E1B, and DCPS were identified as prognostic hub genes and potential therapeutic agents were identified based on these genes. Conclusion The m7G-related gene-based prognostic model showed good prognostic discrimination. Understanding how m7G modification affect the infiltration of the tumor microenvironment (TME) cells will enable us to better understand the TME’s anti-tumor immune response, and hopefully guide more effective immunotherapy methods.
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Affiliation(s)
- Xin-yu Li
- Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Shou-lian Wang
- Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - De-hu Chen
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital), Taizhou, China
| | - Hui Liu
- Department of Clinical Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Jian-Xiong You
- Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li-xin Su
- Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xi-tao Yang
- Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Xi-tao Yang,
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Liu P, Li H, Liao C, Tang Y, Li M, Wang Z, Wu Q, Zhou Y. Identification of key genes and biological pathways in Chinese lung cancer population using bioinformatics analysis. PeerJ 2022; 10:e12731. [PMID: 35178291 PMCID: PMC8812315 DOI: 10.7717/peerj.12731] [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: 05/07/2021] [Accepted: 12/11/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Identification of accurate prognostic biomarkers is still particularly urgent for improving the poor survival of lung cancer patients. In this study, we aimed to identity the potential biomarkers in Chinese lung cancer population via bioinformatics analysis. METHODS In this study, the differentially expressed genes (DEGs) in lung cancer were identified using six datasets from Gene Expression Omnibus (GEO) database. Subsequently, enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of lung cancer. Protein-protein interaction (PPI) and CytoHubba analysis were performed to determine the hub genes. The GEPIA, Human Protein Atlas (HPA), Kaplan-Meier plotter, and TIMER databases were used to explore the hub genes. The receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of hub genes. Reverse transcription quantitative PCR (qRT-PCR) was used to validate the expression levels of hub genes in 10 pairs of lung cancer paired tissues. RESULTS A total of 499 overlapping DEGs (160 upregulated and 339 downregulated genes) were identified in the microarray datasets. DEGs were mainly associated with pathways in cancer, focal adhesion, and protein digestion and absorption. There were nine hub genes (CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A, UBE2C, CHEK1 and BIRC5) identified by PPI and module analysis. In GEPIA database, the expression levels of these genes in lung cancer tissues were significantly upregulated compared with normal lung tissues. The results of prognostic analysis showed that relatively higher expression of hub genes was associated with poor prognosis of lung cancer. In HPA database, most hub genes were highly expressed in lung cancer tissues. The hub genes have good diagnostic efficiency in lung cancer and normal tissues. The expression of any hub gene was associated with the infiltration of at least two immune cells. qRT-PCR confirmed that the expression level of CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A were highly expressed in lung cancer tissues. CONCLUSIONS The hub genes and functional pathways identified in this study may contribute to understand the molecular mechanisms of lung cancer. Our findings may provide new therapeutic targets for lung cancer patients.
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Affiliation(s)
- Ping Liu
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, China
| | - Hui Li
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, China
| | - Chunfeng Liao
- Department of Cardiology, The First Hospital of Changsha, Changsha, China
| | - Yuling Tang
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, China
| | - Mengzhen Li
- MyGene Diagnostics Co., Ltd., Guangzhou, China
| | - Zhouyu Wang
- MyGene Diagnostics Co., Ltd., Guangzhou, China
| | - Qi Wu
- Department of Emergency, The First Hospital of Changsha, Changsha, China
| | - Yun Zhou
- Department of Spinal Surgery, The First Hospital of Changsha, Changsha, China
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12
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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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Ju X, Tang Y, Qu R, Hao S. The Emerging Role of Circ-SHPRH in Cancer. Onco Targets Ther 2021; 14:4177-4188. [PMID: 34285509 PMCID: PMC8286153 DOI: 10.2147/ott.s317403] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 06/29/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE Circ-SHPRH is a circular RNA that can regulate the expression of target genes by sponging microRNAs (miRNAs) or translating tumor suppressor proteins. Recent studies have suggested that circ-SHPRH may play a role in the development of tumors and cancers. Hence, this paper aimed to review the biological characteristics, molecular mechanisms, and potential clinical significance of circ-SHPRH in a variety of tumors and to evaluate its potential as a new diagnostic and prognostic biomarker. METHODS Numerous experiments were performed regarding the abnormal expression of circ-SHPRH in a variety of tumors, including hepatocellular carcinoma, gastric carcinoma, non-small cell lung cancer, osteosarcoma, colorectal cancer, cholangiocarcinoma, pancreatic ductal adenocarcinoma, retinoblastoma, and glioblastoma. RESULTS Upregulation of circ-SHPRH reportedly inhibits tumor cell proliferation, migration, and invasion, leading to the inhibition of tumor development. The clinicopathological parameters and the functional characteristics of circ-SHPRH in multiple human tumors and cancers were summarized. Circ-SHPRH functions as a tumor suppressor gene and has great potential as a diagnostic and prognostic biomarker for different types of cancer.
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Affiliation(s)
- Xinyue Ju
- Department of Hematology and Oncology, The Second Bethune Clinical Medical College of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Yan Tang
- Department of Hematology and Oncology, The Second Bethune Clinical Medical College of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Rongfeng Qu
- Department of Hematology and Oncology, The Second Bethune Clinical Medical College of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Shuhong Hao
- Department of Hematology and Oncology, The Second Bethune Clinical Medical College of Jilin University, Changchun, Jilin, People’s Republic of China
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Circular RNA PLEC acts as a sponge of microRNA-198 to promote gastric carcinoma cell resistance to paclitaxel and tumorigenesis. Pathol Res Pract 2021; 224:153487. [PMID: 34225215 DOI: 10.1016/j.prp.2021.153487] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/11/2021] [Accepted: 05/15/2021] [Indexed: 01/07/2023]
Abstract
Gastric carcinoma (GC) is one of the most frequent types of malignancy worldwide. Resistance to paclitaxel (PTX) has become an obstacle to the prognosis of GC, and the underlying mechanism is not clear. A previous study identified GC-related circRNAs via microarray analysis and bioinformatics analysis, and we discovered that circPLEC (hsa_circ_104722) was markedly upregulated in GC tissues and cells. The molecular mechanism of circPLEC in PTX-resistant GC cells still needs to be explored. In the present study, qRT-PCR demonstrated that circPLEC was upregulated in PTX-resistant GC tissues and cells, indicating that circPLEC boosts the PTX resistance of GC. circPLEC downregulation weakened GC resistance to PTX and tumorigenesis, migration and invasion and promoted the apoptosis of PTX-resistant GC cells. MiR-198 inhibitor reversed the effect of circPLEC downreguAlation in PTX-resistant GC cells, and MUC19 downregulation weakened GC resistance to PTX and tumorigenesis and improved the apoptosis of PTX-resistant GC cells. In summary, circPLEC acts as a sponge of miR-198 to promote the PTX resistance and tumorigenesis of GC cells by regulating MUC19 expression.
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15
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Cheng Z, Liu G, Huang C, Zhao X. Upregulation of circRNA_100395 sponges miR-142-3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis. Oncol Lett 2021; 21:419. [PMID: 33841580 PMCID: PMC8020390 DOI: 10.3892/ol.2021.12680] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 01/20/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC.
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Affiliation(s)
- Zhiyi Cheng
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Guiyuan Liu
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Chuanjiang Huang
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Xiaojun Zhao
- Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
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Song Y, Tang W, Li H. Identification of KIF4A and its effect on the progression of lung adenocarcinoma based on the bioinformatics analysis. Biosci Rep 2021; 41:BSR20203973. [PMID: 33398330 PMCID: PMC7823194 DOI: 10.1042/bsr20203973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/25/2020] [Accepted: 01/04/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent histological type of lung cancer, and its incidence has displayed an upward trend in recent years. Nevertheless, little is known regarding effective biomarkers for LUAD. METHODS The robust rank aggregation method was used to mine differentially expressed genes (DEGs) from the gene expression omnibus (GEO) datasets. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to extract hub genes from the protein-protein interaction (PPI) network. The expression of the hub genes was validated using expression profiles from TCGA and Oncomine databases and was verified by real-time quantitative PCR (qRT-PCR). The module and survival analyses of the hub genes were determined using Cytoscape and Kaplan-Meier curves. The function of KIF4A as a hub gene was investigated in LUAD cell lines. RESULTS The PPI analysis identified seven DEGs including BIRC5, DLGAP5, CENPF, KIF4A, TOP2A, AURKA, and CCNA2, which were significantly upregulated in Oncomine and TCGA LUAD datasets, and were verified by qRT-PCR in our clinical samples. We determined the overall and disease-free survival analysis of the seven hub genes using GEPIA. We further found that CENPF, DLGAP5, and KIF4A expressions were positively correlated with clinical stage. In LUAD cell lines, proliferation and migration were inhibited and apoptosis was promoted by knocking down KIF4A expression. CONCLUSION We have identified new DEGs and functional pathways involved in LUAD. KIF4A, as a hub gene, promoted the progression of LUAD and might represent a potential therapeutic target for molecular cancer therapy.
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Affiliation(s)
- Yexun Song
- Department of Otolaryngology-Head Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Wenfang Tang
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha 410000, Hunan Province, China
| | - Hui Li
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha 410000, Hunan Province, China
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17
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Hong Z, Wang Q, Hong C, Liu M, Qiu P, Lin R, Lin X, Chen F, Li Q, Liu L, Wang C, Chen D. Identification of Seven Cell Cycle-Related Genes with Unfavorable Prognosis and Construction of their TF-miRNA-mRNA regulatory network in Breast Cancer. J Cancer 2021; 12:740-753. [PMID: 33403032 PMCID: PMC7778540 DOI: 10.7150/jca.48245] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 11/04/2020] [Indexed: 12/24/2022] Open
Abstract
Breast cancer (BC), with complex tumorigenesis and progression, remains the most common malignancy in women. We aimed to explore some novel and significant genes with unfavorable prognoses and potential pathways involved in BC initiation and progression via bioinformatics methods. BC tissue-specific microarray datasets of GSE42568, GSE45827 and GSE54002, which included a total of 651 BC tissues and 44 normal breast tissues, were obtained from the Gene Expression Omnibus (GEO) database, and 124 differentially expressed genes (DEGs) were identified between BC tissues and normal breast tissues via R software and an online Venn diagram tool. Database for Annotation, Visualization and Integration Discovery (DAVID) software showed that 65 upregulated DEGs were mainly enriched in the regulation of the cell cycle, and Search Tool for the Retrieval of Interacting Genes (STRING) software identified the 39 closest associated upregulated DEGs in protein-protein interactions (PPIs), which validated the high expression of genes in BC tissues by the Gene Expression Profiling Interactive Analysis (GEPIA) tool. In addition, 36 out of 39 BC patients showed significantly worse outcomes by Kaplan-Meier plotter (KM plotter), and an additional Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that seven genes (cyclin E2 (CCNE2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), mitotic checkpoint serine/threonine kinase B (BUB1B), dual-specificity protein kinase (TTK), cell division cycle 20 (CDC20), and pituitary tumor transforming gene 1 (PTTG1)) were markedly enriched in the cell cycle pathway. Analysis of the clinicopathological characteristics of hub genes revealed that seven cell cycle-related genes (CCRGs) were significantly highly expressed in four BC subtypes (luminal A, luminal B, HER2-positive and triple-negative (TNBC)), and except for the CCNE2 gene, high expression levels were significantly associated with tumor pathological grade and stage and metastatic events of BC. Furthermore, genetic mutation analysis indicated that genetic alterations of CCRGs could also significantly affect BC patients' prognosis. A quantitative real-time polymerase chain reaction (qRT-PCR) assay found that the seven CCRGs were significantly differentially expressed in BC cell lines. Integration of published multilevel expression data and a bioinformatics computational approach were used to predict and construct a regulation mechanism: a transcription factor (TF)-microRNA (miRNA)-messenger RNA (mRNA) regulation network. The present work is the first to construct a regulatory network of TF-miRNA-mRNA in BC for CCRGs and provides new insights into the molecular mechanism of BC.
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Affiliation(s)
- Zhipeng Hong
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China.,Department of Breast Surgery and General Surgery, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350001, P. R. China.,Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian Province, 350001, P.R. China
| | - Qinglan Wang
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Chengye Hong
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Meimei Liu
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Pengqin Qiu
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Rongrong Lin
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Xiaolan Lin
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Fangfang Chen
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Qiuhuang Li
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Lingling Liu
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
| | - Chuan Wang
- Department of Breast Surgery and General Surgery, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350001, P. R. China.,Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian Province, 350001, P.R. China
| | - Debo Chen
- Department of Breast Surgery, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, P. R. China
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Kui L, Tang M. Overview of Computational Methods and Resources for Circular RNAs. SYSTEMS MEDICINE 2021. [DOI: 10.1016/b978-0-12-801238-3.11638-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Wang M, Gong Z, Zhao X, Yu W, Huang F, Dong H. Circular RNAs emerge as important regulators with great potential for clinical application in gastric cancer. Biomark Med 2021; 15:69-82. [PMID: 33185463 DOI: 10.2217/bmm-2020-0591] [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: 09/10/2020] [Accepted: 10/28/2020] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer (GC) is a common digestive malignancy with a high-ranking morbidity and mortality. Therefore, it is urgent to identify novel indicators and develop new strategies for clinical diagnosis and treatment of GC. As a type of noncoding RNA, circular RNAs (circRNAs) have received increased attention in GC during recent years. To more comprehensively understand current research progress on circRNAs in GC, in this review, we introduce basic knowledge of circRNAs, summarize abnormally expressed circRNAs and discuss their functions and regulatory molecular mechanisms in GC. Then, we review potential applications of circRNAs for GC diagnosis, prognosis and treatment. Finally, we conclude by highlighting major advancements of circRNAs in GC research, and we discuss existing challenges and possible future research directions of GC-associated circRNAs.
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Affiliation(s)
- Mei Wang
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Zheng Gong
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Xinxin Zhao
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Wanjun Yu
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Feng Huang
- Department of Clinical Laboratory, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu Province 215300, China
| | - Haibo Dong
- Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu Province 210008, China
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Ma B, Zhao H, Gong L, Xiao X, Zhou Q, Lu H, Cui Y, Xu H, Wu S, Tang Y, Ye Y, Gu W, Li X. Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia. Placenta 2020; 103:232-241. [PMID: 33202359 DOI: 10.1016/j.placenta.2020.10.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/02/2020] [Accepted: 10/09/2020] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Circular RNAs (circRNAs) are non-coding RNAs that are implicated in preeclampsia (PE) pathogenesis; however, their expression and functions in PE remain unclear. In this study, we aimed to investigate the expression of circRNAs in PE and construct a competing endogenous RNA (ceRNA) network, and analyze the associated pathways in PE pathogenesis. METHODS We performed circRNA sequencing to identify the differential expression profile of circRNAs in PE as compared to normal pregnancy. The circRNA candidates were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Subsequently, we used datasets from the GEO database to generate the interaction network between circRNAs, microRNAs (miRNAs), and mRNAs. GO and KEGG enrichment analyses were performed to understand the functional significance of the differentially expressed circRNAs in PE. RESULTS We identified 361 differentially expressed circRNAs (252 upregulated and 109 downregulated) in preeclamptic placentas. Within the selected 31 circRNAs, 6 of them were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these circRNAs, e.g., T cell receptor signaling and MAP kinase pathways. A total of 134 miRNAs and 199 mRNAs were revealed to be differentially expressed in PE by analyzing datasets from the GEO database. The circRNA-miRNA-mRNA network comprised 206 circRNAs, 50 miRNAs, and 38 mRNAs. KEGG analysis of the 38 mRNAs included pathways involved in AMPK and PI3K-Akt signaling. DISCUSSION Our results reported the differential expression profile of circRNAs and the circRNA-miRNA-mRNA network in PE, which provides potential therapeutic targets for this disease.
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Affiliation(s)
- Bo Ma
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Huanqiang Zhao
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Lili Gong
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Xirong Xiao
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Qiongjie Zhou
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Huiqing Lu
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Yutong Cui
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Huangfang Xu
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Suwen Wu
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Yao Tang
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Yunzhen Ye
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China
| | - Weirong Gu
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
| | - Xiaotian Li
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China; The Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China; The Shanghai Key Laboratory of Birth Defects, Shanghai, China; Institutes of Biochemical Sciences, Fudan University, Shanghai, China.
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Identification of Key Genes in Gastric Cancer by Bioinformatics Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7658230. [PMID: 33015179 PMCID: PMC7525308 DOI: 10.1155/2020/7658230] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 08/12/2020] [Accepted: 09/01/2020] [Indexed: 12/22/2022]
Abstract
Gastric cancer (GC) is one of the most common malignancies of the digestive system with few genetic markers for its early detection and prevention. In this study, differentially expressed genes (DEGs) were analyzed using GEO2R from GSE54129 and GSE13911 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING, and Cytoscape. Finally, we performed survival analysis of key genes through the Kaplan-Meier plotter. A total of 1034 DEGs were identified in GC. GO and KEGG results showed that DEGs mainly enriched in plasma membrane, cell adhesion, and PI3K-Akt signaling pathway. Subsequently, the PPI network with 44 nodes and 333 edges was constructed, and 18 candidate genes in the network were focused on by centrality analysis and module analysis. Furthermore, data showed that high expressions of fibronectin 1(FN1), the tissue inhibitor of metalloproteinases 1 (TIMP1), secreted phosphoprotein 1 (SPP1), apolipoprotein E (APOE), and versican (VCAN) were related to poor overall survivals in GC patients. In summary, this study suggests that FN1, TIMP1, SPP1, APOE, and VCAN may act as the key genes in GC.
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Comprehensive Analysis of a circRNA-miRNA-mRNA Network to Reveal Potential Inflammation-Related Targets for Gastric Adenocarcinoma. Mediators Inflamm 2020; 2020:9435608. [PMID: 32801999 PMCID: PMC7416288 DOI: 10.1155/2020/9435608] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 05/28/2020] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.
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Geng H, Li K, Pan Q, Tao S, Li C, Zhao H, Zhao X. Identification and Expression of Several Circular RNAs and Knockdown of hsa_circ_0005556 Exerts Oncogenic Functions by miR-767-5p in Gastric Cancer. Med Sci Monit 2020; 26:e921163. [PMID: 32728015 PMCID: PMC7412919 DOI: 10.12659/msm.921163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) remains one of the most fatal digestive cancers in the world; nevertheless, its etiology remains vague. With the development of bioinformatics analysis, numerous circular RNAs (circRNAs) have been found to be dysregulated in GC. However, the functions of a large portion of dysregulated circRNAs in GC need further validation. In this study, we aimed to validate the biological functions of circ_0005556, which was previously identified to be dysregulated in GC. MATERIAL AND METHODS Levels of circRNAs and miRNAs in GC tissues and cells were estimated by qRT-PCR. The target miRNAs of circ_0005556 were predicted by bioinformatics methods. The interplay between circ_0005556 and miR-767-5p was validated by dual-luciferase reporter and circRNA immunoprecipitation assays. The effects of circ_0005556 and miR-767-5p on GC cell viability, apoptosis, migration, and invasion were assessed by MTT, flow cytometry, wound-healing and in vitro transwell experiments, respectively. RESULTS The upregulation of circ_0005556 was validated by qRT-PCR in GC tissues and cells, and a higher circ_0005556 level indicated a poorer prognosis. miR-767-5p was demonstrated to target circ_0005556 in GC cells, and a negative correlation was found between their expression levels in GC tissues. Knockdown of circ_0005556 promoted miR-767-5p expression in GC cells. Knockdown of circ_0005556 was revealed to repress GC cell viability, invasion, and migration and to promote GC cell apoptosis. Moreover, overexpression of miR-767-5p could significantly augment the repressive impacts of circ_0005556 knockdown on GC cell progression in vitro. CONCLUSIONS The in vitro knockdown of circ_0005556 remarkably repressed GC cell progression by increasing the expression of miR-767-5p.
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Affiliation(s)
- Hanke Geng
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Kaixuan Li
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Qi Pan
- Imaging Department, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Shaohui Tao
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Chunjuan Li
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Haiwei Zhao
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
| | - Xiaojun Zhao
- Clinical Laboratory, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China (mainland)
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Wang Y, Zhang J, Chen X, Gao L. Circ_0001023 Promotes Proliferation and Metastasis of Gastric Cancer Cells Through miR-409-3p/PHF10 Axis. Onco Targets Ther 2020; 13:4533-4544. [PMID: 32547084 PMCID: PMC7250310 DOI: 10.2147/ott.s244358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 04/02/2020] [Indexed: 12/14/2022] Open
Abstract
Background Circular RNAs (circRNAs) have been well documented to regulate the gene expression via sponging microRNA (miRNA) in diverse neoplasms including gastric cancer (GC). Methods In the present study, the expressions of circ_0001023, miR-409-3p, and plant homeodomain finger 10 (PHF10) in GC tissues were detected by qRT-PCR. Chi-square test was performed to analyze the associations between circ_0001023 and pathological parameters. Cell Counting Kit-8 assay, colony formation assay, flow cytometry, and transwell assay were adopted to detect the role of circ_0001023/miR-409-3p axis in the proliferation, apoptosis, and migration of GC cells, respectively. The targeting relationship between circ_0001023 and miR-409-3p was investigated by dual-luciferase gene reporter gene assay. Additionally, subcutaneous xenotransplanted tumor model in nude mice was established to detect the function of circ_0001023 on GC growth in vivo. Results Compared with adjacent tissues, the expression of circ_0001023 was significantly upregulated and correlated with lymph node invasion and higher T stage of GC patients. It has also been proved that circ_0001023 could target miR-409-3p. Silencing circ_0001023 can impede the proliferation of GC cells and promote apoptosis, while miR-409-3p inhibitors can partially reverse the biological behavior of GC cells mentioned above. Moreover, the expression of circ_0001023 was reversely associated with miR-409-3p expression but positively correlated with PHF10, a downstream oncogene of miR-409-3p. Conclusion Collectively, it is concluded that circ_0001023 promotes the progression of GC via regulating miR-409-3p/PHF10 axis.
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Affiliation(s)
- Yongxiang Wang
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, Zhejiang Province, People's Republic of China
| | - Jianbin Zhang
- Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China.,Department of Oncology, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Xiaochen Chen
- Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China.,Department of Oncology, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Liang Gao
- Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou 310022, Zhejiang Province, People's Republic of China.,Department of Oncology, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
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25
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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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Wen C, Xu G, He S, Huang Y, Shi J, Wu L, Zhou H. Screening Circular RNAs Related to Acquired Gefitinib Resistance in Non-small Cell Lung Cancer Cell Lines. J Cancer 2020; 11:3816-3826. [PMID: 32328186 PMCID: PMC7171488 DOI: 10.7150/jca.39783] [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: 08/30/2019] [Accepted: 03/27/2020] [Indexed: 12/25/2022] Open
Abstract
Background: Gefitinib is a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) used to treat EGFR mutation-positive patients with non-small cell lung cancer (NSCLC). However, the efficacy of gefitinib is limited by the development of acquired resistance. Studies have shown that circular RNAs (circRNAs) are involved in the acquired resistance to many anticancer agents. However, the expression profiles and functions of circRNAs in gefitinib resistance in NSCLC are poorly understood so far. Methods: In this study, circRNA expression profiling was explored in two gefitinib-resistant NSCLC cell lines (HCC827/GR and PC9/GR) and their parental sensitive cells (HCC827 and PC9) using high-throughput RNA sequencing. Quantitative real-time PCR (qRT-PCR) was used to confirm the expression of selected differentially expressed circRNAs. Bioinformatic tools including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), network analysis, and Kaplan-Meier plotter database were used to predict the functions and pathways of these differentially expressed circRNAs. Results: We identified 46 and 56 differentially expressed circRNAs in HCC827/GR and PC9/GR cell lines, respectively, compared with those in their parental cell lines. Gene ontology and KEGG pathway analysis identified that the host linear transcripts of these differentially expressed circRNAs were involved in many critical biological pathways and molecular functions. We found that hsa_circ_0000567 was consistently up-regulated, and hsa_circ_0006867 was consistently down-regulated in two resistant cell lines. We further used hsa_circ_0000567 and hsa_circ_0006867 as key circRNAs to construct circRNA-miRNA-mRNA networks. Several target mRNAs of these two circRNAs had been shown to significantly associate with the overall survival of patients with lung cancer. Conclusions: In this study, we generated the comprehensive expression and functional profiles of the differentially expressed circRNAs between gefitinib-resistant and -sensitive NSCLC cells, and showed that dysregulation of circRNAs might play an important role in the development of acquired resistance to gefitinib in NSCLC.
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Affiliation(s)
- Chunjie Wen
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Ge Xu
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Shuai He
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Yutang Huang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Jingjing Shi
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Lanxiang Wu
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Honghao Zhou
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China.,Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, China
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Xiang S, Li Z, Weng X. Changed cellular functions and aberrantly expressed miRNAs and circRNAs in bone marrow stem cells in osteonecrosis of the femoral head. Int J Mol Med 2020; 45:805-815. [PMID: 31922208 PMCID: PMC7015133 DOI: 10.3892/ijmm.2020.4455] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 05/15/2019] [Indexed: 02/06/2023] Open
Abstract
The present study aimed to detect the correlations between altered cellular functions in bone marrow stem cells (BMSCs) and osteonecrosis of the femoral head (ONFH). By profiling the aberrant expression of miRNAs and circRNAs in BMSCs isolated from ONFH patients, the present study aimed to further explore the potential regulatory mechanisms of action of circRNAs in ONFH using integrated bioinfor-matics analysis. BMSCs were isolated from seven ONFH patients and seven controls. Cellular functions, including proliferation, apoptosis and differentiation, were compared. miRNA and circRNA sequencing were conducted using RNA samples of three ONFH patients and three controls to identify differentially expressed circRNAs and miRNAs. The expression of hsa_circ_0000219, hsa_circ_0004588 and hsa_circ_0005936 were validated by qPCR. Target miRNAs were also predicted and validated by qPCR and circRNA-miRNA co-expression networks were constructed. BMSCs of ONFH patients displayed decreased proliferation and increased apoptosis during in vitro culturing. In addition, reduced osteogenesis and enhanced adipogenesis were found in the ONFH group. A total of 129 miRNAs and 231 circRNAs were detected to be differentially expressed. The expression levels of hsa_circ_0000219, hsa_circ_0004588 and hsa_circ_0005936 were significantly decreased in BMSCs of ONFH patients. A number of target miRNAs related to cell proliferation, apoptosis and differentiation were predicted for hsa_circ_0000219 and hsa_circ_0005936. The expression levels of miR-144-3p and miR-1270 were found to be elevated in ONFH patients, which was consistent with miRNA sequencing data and competitive endogenous RNA hypothesis. Time-dependent expression patterns of hsa_circ_0000219, hsa_circ_0004588, hsa_circ_0005936, miR-144-3p and miR-1270 were also validated during osteogenic and adipogenic differentiation in BMSCs. The results of the present study substantiated the involvement of BMSCs in ONFH development. hsa_circ_0000219 and hsa_circ_0005936 may regulate the progression of ONFH by mediating the proliferation and differentiation of BMSCs by sponging miRNAs.
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Affiliation(s)
- Shuai Xiang
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, P.R. China
| | - Zeng Li
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, P.R. China
| | - Xisheng Weng
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, P.R. China
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Guo Y, Huang Q, Zheng J, Hsueh CY, Huang J, Yuan X, Chen H, Zhou L. Diagnostic Significance of Downregulated circMORC3 as a Molecular Biomarker of Hypopharyngeal Squamous Cell Carcinoma: A Pilot Study. Cancer Manag Res 2020; 12:43-49. [PMID: 32021421 PMCID: PMC6954084 DOI: 10.2147/cmar.s235888] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022] Open
Abstract
Background Circular RNAs (circRNAs) have proven to be of great clinical significance as diagnostic biomarkers in various cancers. Here, we investigate the expression of circMORC3 in hypopharyngeal squamous cell carcinoma (HSCC), exploring whether it could serve as a diagnostic marker of HSCC. Methods CircMORC3 expression levels were detected in HSCC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between circMORC3 expression levels and clinicopathologic factors were explored. CircMORC3 expression levels in plasma from HSCC patients and non-tumor patients were also detected by qRT-PCR. Finally, receiver operating characteristic (ROC) curves were established to evaluate the diagnostic value of circMORC3 as a potential HSCC biomarker in tissues and plasma. Results The expression levels of circMORC3 were significantly lower in HSCC tissues than paired adjacent normal tissues, and the area under the ROC curve was 0.834. The decreased expression of circMORC3 was correlated to T stages and tumor sizes. Similarly, the circMORC3 expression levels in HSCC patient plasma were lower than non-tumor patient plasma, and the area under the ROC curve was 0.767. Conclusion Our results indicate that circMORC3 was downregulated in HSCC tissues and plasma, and it could serve as an early diagnostic HSCC biomarker.
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Affiliation(s)
- Yang Guo
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Qiang Huang
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Juan Zheng
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Chi-Yao Hsueh
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Jiameng Huang
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Xiaohui Yuan
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Hui Chen
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
| | - Liang Zhou
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China
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Chi Y, Luo Q, Song Y, Yang F, Wang Y, Jin M, Zhang D. Circular RNA circPIP5K1A promotes non‐small cell lung cancer proliferation and metastasis through miR‐600/HIF‐1α regulation. J Cell Biochem 2019; 120:19019-19030. [PMID: 31241217 DOI: 10.1002/jcb.29225] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 06/06/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Yongbing Chi
- Clinical LaboratoryShanghai Pudong New Area Gongli Hospital Shanghai China
| | - Qiancheng Luo
- Department of Emergency Medicine, Shanghai Pudong New Area Gongli HospitalThe Second Military Medical University Shanghai China
| | - Yuting Song
- Ningxia Medical University Ningxia China
- Sino‐French Cooperative Central Lab, Shanghai Gongli HospitalSecondary Military Medical University Shanghai China
| | - Fangsong Yang
- Anhui Gaolu Winery Staff Hospital Bozhou Shanghai China
| | - Ying Wang
- Department of Central Laboratory, Shanghai Gongli HospitalThe Second Military Medical University Shanghai China
| | - Mingming Jin
- Department of Central Laboratory, Shanghai Gongli HospitalThe Second Military Medical University Shanghai China
| | - Denghai Zhang
- Department of Central Laboratory, Shanghai Gongli HospitalThe Second Military Medical University Shanghai China
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Wang KW, Dong M. Role of circular RNAs in gastric cancer: Recent advances and prospects. World J Gastrointest Oncol 2019; 11:459-469. [PMID: 31236197 PMCID: PMC6580317 DOI: 10.4251/wjgo.v11.i6.459] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 04/06/2019] [Accepted: 04/19/2019] [Indexed: 02/05/2023] Open
Abstract
Circular RNA (circRNA) is a newly discovered non-coding RNA with special structure, which is widely expressed in eukaryotic organisms and mainly located in the cytoplasm. circRNAs participate in gene regulation by working as miRNA sponges that block the inhibitory effect of miRNA on its target genes. In addition, circRNAs can bind to RNA binding proteins to regulate gene expression. Based on characteristics of stability, expression specificity and participation in gene regulation, circRNAs are expected to be biomarkers for early diagnosis of cancer or potential targets for cancer therapy. With the help of bioinformatics analysis, circRNA microarray analysis and high-throughput sequencing technology, more circRNAs were discovered to participate in the progression of gastric cancer (GC) over the past three years. This article gives an overview of these recent research focusing on the roles of circRNAs in GC and highlights the advances.
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Affiliation(s)
- Ke-Wei Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Ming Dong
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Huang Y, Zhang Y, Jia L, Liu C, Xu F. Circular RNA ABCB10 promotes tumor progression and correlates with pejorative prognosis in clear cell renal cell carcinoma. Int J Biol Markers 2019; 34:176-183. [PMID: 31106654 DOI: 10.1177/1724600819842279] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Our study aimed to evaluate the effect of circular RNA ABCB10 (circ-ABCB10) on proliferation and apoptosis of clear cell renal cell carcinoma (ccRCC) cells, and its prognostic value in patients with ccRCC. METHODS Circ-ABCB10 expression in five ccRCC cell lines and normal kidney epithelial cell line was measured by quantitative polymerase chain reaction (qPCR). Empty overexpression, circ-ABCB10 overexpression, empty shRNA, and circ-ABCB10 shRNA plasmids were transfected into A498 cells as negative control for circ-ABCB10 over expression {NC (+)}, Circ-ABCB10(+), negative control (-){NC(-)}, and Circ-ABCB10(-) groups, then cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 and annexin V/propidium iodide. Meanwhile, apoptotic markers were measured by western blot. Subsequently, circ-ABCB10 expression in tumor tissues and paired adjacent tissues from 120 ccRCC patients was measured by qPCR. RESULTS Circ-ABCB10 expression was elevated in all the ccRCC cell lines compared with the normal kidney cells line. A498 cell proliferation was enhanced in the Circ-ABCB10(+) group compared with the NC(+) group, while it was inhibited in the Circ-ABCB10(-) group compared with the NC (-) group; and A498 cell apoptosis was repressed in the Circ-ABCB10(+) group than the NC(+) group, but was promoted in the Circ-ABCB10(-) group compared with the NC(-) group. In addition, circ-ABCB10 was up-regulated in tumor tissues compared with paired adjacent tissues, and its high expression correlated with the advanced pathological grade and the tumor node metastasis stage as well as independently predicting worse overall survival in ccRCC patients. CONCLUSION Circ-ABCB10 promotes tumor progression and correlates with pejorative prognosis in ccRCC.
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Affiliation(s)
- Yunfang Huang
- 1 Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yun Zhang
- 2 Department of Nephrology, The Sixth Hospital of Wuhan, Wuhan, China
| | - Lin Jia
- 1 Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Changxuan Liu
- 1 Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fang Xu
- 1 Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Li X, He M, Guo J, Cao T. Upregulation of circular RNA circ-ERBB2 predicts unfavorable prognosis and facilitates the progression of gastric cancer via miR-503/CACUL1 and miR-637/MMP-19 signaling. Biochem Biophys Res Commun 2019; 511:926-930. [DOI: 10.1016/j.bbrc.2019.03.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 03/02/2019] [Indexed: 12/30/2022]
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Zhang X, Liu F, Bai P, Dong N, Chu C. Identification of key genes and pathways contributing to artery tertiary lymphoid organ development in advanced mouse atherosclerosis. Mol Med Rep 2019; 19:3071-3086. [PMID: 30816519 PMCID: PMC6423582 DOI: 10.3892/mmr.2019.9961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 02/12/2019] [Indexed: 01/13/2023] Open
Abstract
Atherosclerosis is a leading cause of mortality worldwide. Artery tertiary lymphoid organ (ATLO) neogenesis is affected by abdominal aorta atherosclerosis, which may lead to an immune response. The present study obtained microarray data to investigate the gene expression differences underlying the potential pathogenesis of atherosclerosis and to elucidate the mechanisms underlying ATLO development. Microarray studies of the aorta, plaques, adventitia, blood, spleen, renal lymph nodes and ATLO were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in aorta clusters and ATLO clusters. Kyoto Encyclopedia of Genes and Genomes enrichment and Gene Ontology (GO) analyses were conducted to predict the biological functions of DEGs. The results demonstrated that interleukin 7 receptor (Il7r), C‑X‑C motif chemokine ligand (Cxcl)16, Cxcl13, Cxcl12, C‑C motif chemokine receptor 2, C‑C motif chemokine ligand (Ccl)8, Ccl5 and Ccl12 may function through pathways associated with 'cytokine‑cytokine receptor interaction' and 'chemokine signaling pathway' in ATLO. Gene expression alterations were validated by reverse transcription‑quantitative polymerase chain reaction. Il7r appeared to be the central gene involved in these events, and chemokines and/or chemokine receptors were visualized by GO enrichment. A protein‑protein interaction network was constructed, which suggested that Il7r had a core function in all clusters. Taken together, the results indicated that Il7r upregulation may serve an important role in ATLO development via 'cytokine‑cytokine receptor interaction' and 'chemokine signaling pathway'. This may provide novel perspectives for understanding ATLO development and the regulation of the immune response in atherosclerosis.
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Affiliation(s)
- Xi Zhang
- Institute for Cardiovascular Prevention, Ludwig‑Maximilians University Munich, D‑80336 Munich, Germany
| | - Fayuan Liu
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Peng Bai
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Nianguo Dong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Chong Chu
- Institute for Cardiovascular Prevention, Ludwig‑Maximilians University Munich, D‑80336 Munich, Germany
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Shi P, Wan J, Song H, Ding X. The emerging role of circular RNAs in gastric cancer. Am J Cancer Res 2018; 8:1919-1932. [PMID: 30416845 PMCID: PMC6220139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 09/08/2018] [Indexed: 06/09/2023] Open
Abstract
Gastric cancer (GC) ranks as the fourth most common cancer and the third leading cause of cancer-related death worldwide. Circular RNAs (circRNAs) are a new class of long noncoding RNAs characterized by a single-stranded covalently closed loop structure. Emerging evidence reveals the essential function of circRNAs in the occurrence and development of human diseases. Among these, circRNAs are aberrantly expressed in GC and are involved in the progression of GC. In this review, we briefly summarize the current knowledge of the classification, biogenesis and biological functions of circRNAs, with an emphasis on their relationship with GC. As our understanding of the relation between circRNAs and GC advances, more diagnostic and therapeutic protocols will be developed for the prevention and treatment of GC.
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Affiliation(s)
- Peina Shi
- The Medical School of Ningbo UniversityNingbo, Zhejiang, China
- The Gastroenterology Department of Ningbo First HospitalNingbo, Zhejiang, China
| | - Jiangnan Wan
- The Medical School of Ningbo UniversityNingbo, Zhejiang, China
- The Gastroenterology Department of Ningbo First HospitalNingbo, Zhejiang, China
| | - Haojun Song
- The Gastroenterology Department of Ningbo First HospitalNingbo, Zhejiang, China
| | - Xiaoyun Ding
- The Gastroenterology Department of Ningbo First HospitalNingbo, Zhejiang, China
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