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Hushmandi K, Klionsky DJ, Farahani N, Reiter RJ, Imani Fooladi AAI, Alimohammadi M, Aref AR. Regulation of pyroptosis in diabetic nephropathy by long non-coding and circular RNAs. Clin Exp Med 2025; 25:208. [PMID: 40531430 PMCID: PMC12176935 DOI: 10.1007/s10238-025-01740-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Accepted: 05/19/2025] [Indexed: 06/22/2025]
Abstract
Diabetic nephropathy (DN) is a major complication of diabetes mellitus, predominantly affecting the kidneys of diabetic patients and resulting in increased morbidity and mortality. Current standard treatments for diabetes have proven insufficient in halting the progression of DN, highlighting the urgent need for innovative and more effective therapeutic strategies. Pyroptosis, a pro-inflammatory regulated cell death process, has been previously associated with DN development. Recent evidence indicates that the NLRP3 inflammasome, a key inflammatory pathway complex, promotes DN through pyroptosis. Consequently, inhibiting inflammasome activity has emerged as a promising therapeutic target against DN, in conjunction with pyroptosis. This review introduces non-coding RNAs (ncRNAs), particularly circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), as potential regulators of pyroptosis in DN, as recent studies have documented their dysregulation in DN pathogenesis. In this study, we aim to discuss the characteristics of lncRNAs, circRNAs, and pyroptosis and explore their potential interconnection in DN development. By elucidating the link between these RNA molecules and pyroptosis, our goal is to deepen our understanding of the underlying mechanisms of the disease. This knowledge could lead to the identification of new therapeutic targets and the development of innovative treatments for DN by modulating pyroptosis.
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Affiliation(s)
- Kiavash Hushmandi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Daniel J Klionsky
- Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Najma Farahani
- Farhikhtegan Medical Convergence sciences Research Center , Farhikhtegan Hospital ,TMs.C., Islamic Azad University, Tehran, Iran
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, TX, USA
| | - Abbas Ali Imani Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Reza Aref
- Department of Vitro Vision, DeepkinetiX, Inc, Boston, MA, USA
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Peng L, Li H, Yuan S, Meng T, Chen Y, Fu X, Cao D. metaCDA: A Novel Framework for CircRNA-Driven Drug Discovery Utilizing Adaptive Aggregation and Meta-Knowledge Learning. J Chem Inf Model 2025; 65:2129-2144. [PMID: 39937612 DOI: 10.1021/acs.jcim.4c02193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2025]
Abstract
In the emerging field of RNA drugs, circular RNA (circRNA) has attracted much attention as a novel multifunctional therapeutic target. Delving deeper into the intricate interactions between circRNA and disease is critical for driving drug discovery efforts centered around circRNAs. Current computational methods face two significant limitations: a lack of aggregate information in heterogeneous graph networks and a lack of higher-order fusion information. To this end, we present a novel approach, metaCDA, which utilizes meta-knowledge and adaptive aggregate learning to improve the accuracy of circRNA and disease association predictions and addresses the limitations of both. We calculate multiple similarity measures between disease and circRNA, construct a heterogeneous graph based on these, and apply meta-networks to extract meta-knowledge from the heterogeneous graph, so that the constructed heterogeneous maps have adaptive contrast enhancement information. Then, we construct a nodal adaptive attention aggregation system, which integrates a multihead attention mechanism and a nodal adaptive attention aggregation mechanism, so as to achieve accurate capture of higher-order fusion information. We conducted extensive experiments, and the results show that metaCDA outperforms existing state-of-the-art models and can effectively predict disease-associated circRNA, opening up new prospects for circRNA-driven drug discovery.
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Affiliation(s)
- Li Peng
- School of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan 411100, China
| | - Huaping Li
- School of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan 411100, China
| | - Sisi Yuan
- Department of Bioinformatics and Genomics, the University of North Carolina at Charlotte, Charlotte, North Carolina 28223-0001, United States
| | - Tao Meng
- College of Computer and Mathematics, Central South University of Forestry and Technology, Changsha, Hunan 410004, China
| | - Yifan Chen
- Institute of Artificial Intelligence Application, College of Computer and Mathematics, Central South University of Forestry and Technology, Changsha, Hunan 410004, P. R. China
| | - Xiangzheng Fu
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR 999077, China
| | - Dongsheng Cao
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410003, China
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Sharma A, Bansal C, Sharma KL, Kumar A. Circular RNA: The evolving potential in the disease world. World J Med Genet 2024; 12:93011. [DOI: 10.5496/wjmg.v12.i1.93011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/23/2024] [Accepted: 07/02/2024] [Indexed: 09/19/2024] Open
Abstract
Circular RNAs (circRNAs), a new star of noncoding RNAs, are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome. Most circRNAs are conserved throughout species and frequently show stage-specific expression during various stages of tissue development. CircRNAs were a mystery discovery, as they were initially believed to be a product of splicing errors; however, subsequent research has shown that circRNAs can perform various functions and help in the regulation of splicing and transcription, including playing a role as microRNA (miRNA) sponges. With the application of high throughput next-generation technologies, circRNA hotspots were discovered. There are emerging indications that explain the association of circRNAs with human diseases, like cancers, developmental disorders, and inflammation, and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases, including cancer. After the discoveries of miRNAs and long noncoding RNAs, circRNAs are now acting as a novel research entity of interest in the field of RNA disease biology. In this review, we aim to focus on major updates on the biogeny and metabolism of circRNAs, along with their possible/established roles in major human diseases.
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Affiliation(s)
- Aarti Sharma
- Department of Research, Mayo Clinic Arizona, Phoenix, AZ 85054, United States
| | - Cherry Bansal
- Department of Pathology, Dr. S Tantia Medical College, Hospital and Research Center, Sri Ganganagar 335002, Rajasthan, India
| | - Kiran Lata Sharma
- Department of Pathology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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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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Xiao F, He Z, Wang S, Li J, Fan X, Yan T, Yang M, Yang D. Regulatory mechanism of circular RNAs in neurodegenerative diseases. CNS Neurosci Ther 2024; 30:e14499. [PMID: 37864389 PMCID: PMC11017410 DOI: 10.1111/cns.14499] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 08/24/2023] [Accepted: 10/02/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins. AIMS This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases. METHODS We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases. RESULTS Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD. CONCLUSIONS In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.
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Affiliation(s)
- Feng Xiao
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Zhi He
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
| | - Siqi Wang
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Jiamei Li
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Xiaolan Fan
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Taiming Yan
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
| | - Mingyao Yang
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Deying Yang
- College of Animal Science and TechnologySichuan Agricultural UniversityChengduChina
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
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Wu M, Yuan S, Liu K, Wang C, Wen F. Gastric Cancer Signaling Pathways and Therapeutic Applications. Technol Cancer Res Treat 2024; 23:15330338241271935. [PMID: 39376170 PMCID: PMC11468335 DOI: 10.1177/15330338241271935] [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: 03/02/2024] [Revised: 05/31/2024] [Accepted: 06/25/2024] [Indexed: 10/09/2024] Open
Abstract
Gastric cancer (GC) is a prevalent malignant tumor and ranks as the second leading cause of death among cancer patients worldwide. Due to its hidden nature and difficulty in detection, GC has a high incidence and poor prognosis. Traditional treatment methods such as systemic chemotherapy, radiotherapy, and surgical resection are commonly used, but they often fail to achieve satisfactory curative effects, resulting in a very low 5-year survival rate for GC patients. Currently, targeted therapy and immunotherapy are prominent areas of research both domestically and internationally. These methods hold promise for the treatment of GC. This article focuses on the signaling pathways associated with the development of GC, as well as the recent advancements and applications of targeted therapy and immunotherapy. The aim is to provide fresh insights for the clinical treatment of GC.
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Affiliation(s)
- Mingfang Wu
- The Second Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China
| | - Shiman Yuan
- The Clinical Medical College, Guizhou Medical University, Guiyang, China
| | - Kai Liu
- The Clinical Medical College, Guizhou Medical University, Guiyang, China
| | - Chenyu Wang
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Feng Wen
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, China
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Mazloomi S, Mousavi V, Aghadavod E, Mafi A. Circular RNAs: Emerging Modulators in the Pathophysiology of Polycystic Ovary Syndrome and their Clinical Implications. Curr Mol Med 2024; 24:153-166. [PMID: 36627779 DOI: 10.2174/1566524023666230110151155] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 11/17/2022] [Accepted: 11/22/2022] [Indexed: 01/12/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders. Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network. Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.
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Affiliation(s)
- Sahar Mazloomi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Vahide Mousavi
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Biochemistry, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Gong S, Zhang Y, Pang L, Wang L, He W. A novel CircRNA Circ_0001722 regulates proliferation and invasion of osteosarcoma cells through targeting miR-204-5p/RUNX2 axis. J Cancer Res Clin Oncol 2023; 149:12779-12790. [PMID: 37453970 PMCID: PMC10587032 DOI: 10.1007/s00432-023-05166-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/09/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND Osteosarcoma (OS) is the most prevalent primary fatal bone neoplasm in adolescents and children owing to limited therapeutic methods. Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the roles of circRNAs in OS are still unclear. METHODS Firstly, we evaluate the differentially expressed circRNAs in 3 paired OS and corresponding adjacent nontumor tissue samples by circRNA microarray assay, finding a novel circRNA, circ_001722, significantly upregulated in OS tissues and cells. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of OS cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was verified by dual-luciferase assay and RNA immunoprecipitation assay. RESULTS A novel circRNA, circ_001722, is significantly upregulated in OS tissues and cells. Downregulation of circ_0001722 can suppress proliferation and invasion of human OS cells in vitro and in vivo. Computational algorithms predict miR-204-5p can bind with circ_0001722 and RUNX2 mRNA 3'UTR, which is verified by Dual-luciferase assay and RNA immunoprecipitation assay. Further functional experiments show that circ_0001722 competitively binds to miR-204-5p and prevents it to decrease the level of RUNX2, which upregulates proliferation and invasion of human OS cells. CONCLUSION Circ_001722 is a novel tumor promotor in OS, and promotes the progression of OS via miR-204-5p/RUNX2 axis.
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Affiliation(s)
- Shuai Gong
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 of Jianshe Road, Er-Qi District, Zhengzhou City, 450052 Henan Province China
| | - Yi Zhang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan Province China
| | - Lina Pang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 of Jianshe Road, Er-Qi District, Zhengzhou City, 450052 Henan Province China
| | - Liye Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 of Jianshe Road, Er-Qi District, Zhengzhou City, 450052 Henan Province China
| | - Wei He
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 of Jianshe Road, Er-Qi District, Zhengzhou City, 450052 Henan Province China
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Yan L, Yan Q. Serum circRNA_100199 is a Prognostic Biomarker in Acute Myeloid Leukemia. Int J Gen Med 2023; 16:4661-4668. [PMID: 37868816 PMCID: PMC10588716 DOI: 10.2147/ijgm.s426218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/13/2023] [Indexed: 10/24/2023] Open
Abstract
Background An aberrant level of serum microRNA expression has been demonstrated to be a prognostic marker for acute myeloid leukemia (AML). The therapeutic relevance of serum circRNA 100199 remained unknown, however. This research aimed to investigate the probable prognostic significance of serum circRNA_100199 for AML. Methods This study included a total of 200 participants consisting of 114 AML-diagnosed patients and 86 healthy people. Blood samples were taken, and the level of circRNA_100199 in the serum was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to explore its potential clinical significance. Results Our study demonstrated that circRNA_100199 expression in the serum was substantially higher in AML subjects than in healthy persons. This increase in serum circRNA_100199 levels was particularly noticeable in M4/M5 subtype AML patients, and those with poor cytogenetic risk or higher white blood cell counts. Using receiver operating characteristic (ROC) analysis, AML cases were effectively differentiated from healthy persons based on the level of serum circRNA_100199. Furthermore, it was found that high serum circRNA_100199 expression was strongly linked with shorter survival times and more severe clinical features. Our study also confirmed that high serum circRNA_100199 expression was an independent predictor of relapse-free survival (RFS) and overall survival (OS) in AML patients. Interestingly, the serum expression level of circRNA_100199 was significantly reduced following treatment, and its levels were substantially lower in AML patients who achieved complete remission (CR) than those who did not. Conclusion Overall, these findings suggest that serum circRNA_100199 has the potential to be a favorable prognostic biomarker for AML.
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Affiliation(s)
- Lingqiao Yan
- Department of Hematology, the First People’s Hospital of Wenling, Wenling, Zhejiang, 317500, People’s Republic of China
| | - Qingxian Yan
- Department of Hematology, the First People’s Hospital of Wenling, Wenling, Zhejiang, 317500, People’s Republic of China
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Sun P, Chen M, Sooranna SR, Shi D, Liu Q, Li H. The emerging roles of circRNAs in traits associated with livestock breeding. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 14:e1775. [PMID: 36631071 DOI: 10.1002/wrna.1775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 12/22/2022] [Accepted: 12/27/2022] [Indexed: 01/13/2023]
Abstract
Many indicators can be used to evaluate the productivity and quality of livestock, such as meat and milk production as well as fat deposition. Meat and milk production are measures of livestock performance, while fat deposition affects the taste and flavor of the meat. The circRNAs, are non-coding RNAs, that are involved in the regulation of all these three traits. We review the functions and mechanisms of circRNAs in muscle and fat development as well as lactation to provide a theoretical basis for circRNA research in animal husbandry. Various phenotypic changes presented in livestock may be produced by different circRNAs. Our current concern is how to use the roles played by circRNAs to our advantage to produce the best possible livestock. Hence, we describe the advantages and disadvantages of knockout techniques for circRNAs. In addition, we also put forward our thoughts regarding the mechanism and network of circRNAs to provide researchers with novel ideas of how molecular biology can help us advance our goals in animal farming. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
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Affiliation(s)
- Ping Sun
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Mengjie Chen
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Suren R Sooranna
- Institute of Reproductive and Developmental Biology, Imperial College London, London, UK
| | - Deshun Shi
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Qingyou Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan, China
| | - Hui Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China
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Wang Y, Li N, Wu X. Circular RNA_0003800 exacerbates IL-1β-induced chondrocyte injury via miR-197-3p/SOX5 axis. Int Immunopharmacol 2023; 115:109643. [PMID: 36610331 DOI: 10.1016/j.intimp.2022.109643] [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: 09/15/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Osteoarthritis (OA) is a serious degenerative disease of articular cartilage, which has a great impact on the quality of life of patients. Circular RNA (circRNA) plays an important role in OA progression. Our study aims to explore the role and mechanism of circ_0003800 in OA. METHODS Circ_0003800, microRNA-197-3p (miR-197-3p) and SRY-box transcription factor 5 (SOX5) contents were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell Counting Kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, western blot and enzyme-linked immunosorbent assay (ELISA) were deployed to evaluate cell proliferation, apoptosis, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress. Interaction of miR-197-3p and circ_0003800 or SOX5 was evidenced by dual-luciferase reporter system, RNA immunoprecipitation (RIP) and RNA pull down assays. RESULTS OA tissues and model cells had higher abundance of circ_0003800 and SOX5, while miR-197-3p content was lower. Functionally, circ_0003800 knockdown alleviated IL-1β-mediated injury in C28/I2 cells. Mechanistically, circ_0003800 could sponge miR-197-3p, and miR-197-3p could target SOX5. Besides, in-miR-197-3p reversed the suppressive effect of circ_0003800 downregulation on IL-1β-induced C28/I2 cell injury, and SOX5 overexpression could also diminish the inhibitory effect of miR-197-3p on IL-1β-induced C28/I2 cell injury. CONCLUSION Circ_0003800 exacerbates IL-1β-induced chondrocyte injury via miR-197-3p/SOX5 axis.
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Affiliation(s)
- Yongsheng Wang
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, China
| | - Ningbo Li
- Department of Orthopedics, The Affiliated Hospital of Henan University of Chinese Medicine, China
| | - Xuejian Wu
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, China.
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Xu BB, Huang Y, Zheng ED, Wang JY, Zhang CJ, Geng XG, Wang YN, Pan WS. Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer. Heliyon 2023; 9:e13191. [PMID: 36852074 PMCID: PMC9958299 DOI: 10.1016/j.heliyon.2023.e13191] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 01/16/2023] [Accepted: 01/19/2023] [Indexed: 02/05/2023] Open
Abstract
Background Hsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC. Methods The transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted. Results Overall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p. Conclusions Hsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.
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Affiliation(s)
- Bei-Bei Xu
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, China.,Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China.,Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China
| | - Yi Huang
- Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China
| | - En-Dian Zheng
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China
| | - Jing-Ya Wang
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China
| | - Chen-Jing Zhang
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China
| | - Xiao-Ge Geng
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China
| | - Ya-Nan Wang
- Zhejiang University of Technology, Hangzhou, 310000, Zhejiang, China
| | - Wen-Sheng Pan
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, China.,Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China.,People's Hospital of Hangzhou Medical College, Hangzhou, 310000, Zhejiang, China
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Yang D, Xiao F, Li J, Wang S, Fan X, Ni Q, Li Y, Zhang M, Yan T, Yang M, He Z. Age-related ceRNA networks in adult Drosophila ageing. Front Genet 2023; 14:1096902. [PMID: 36926584 PMCID: PMC10012872 DOI: 10.3389/fgene.2023.1096902] [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: 11/26/2022] [Accepted: 02/10/2023] [Indexed: 03/06/2023] Open
Abstract
As Drosophila is an extensively used genetic model system, understanding of its regulatory networks has great significance in revealing the genetic mechanisms of ageing and human diseases. Competing endogenous RNA (ceRNA)-mediated regulation is an important mechanism by which circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) regulate ageing and age-related diseases. However, extensive analyses of the multiomics (circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA) characteristics of adult Drosophila during ageing have not been reported. Here, differentially expressed circRNAs and microRNAs (miRNAs) between 7 and 42-day-old flies were screened and identified. Then, the differentially expressed mRNAs, circRNAs, miRNAs, and lncRNAs between the 7- and 42-day old flies were analysed to identify age-related circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks in ageing Drosophila. Several key ceRNA networks were identified, such as the dme_circ_0009500/dme_miR-289-5p/CG31064, dme_circ_0009500/dme_miR-289-5p/frizzled, dme_circ_0009500/dme_miR-985-3p/Abl, and XLOC_027736/dme_miR-985-3p/Abl XLOC_189909/dme_miR-985-3p/Abl networks. Furthermore, real-time quantitative PCR (qPCR) was used to verify the expression level of those genes. Those results suggest that the discovery of these ceRNA networks in ageing adult Drosophila provide new information for research on human ageing and age-related diseases.
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Affiliation(s)
- Deying Yang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Feng Xiao
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Jiamei Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Siqi Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Xiaolan Fan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Qingyong Ni
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yan Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Mingwang Zhang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Taiming Yan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Mingyao Yang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.,Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Zhi He
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
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Ruan Y, Li Z, Xie Y, Sun W, Guo J. Detecting plasma hsa_circ_0061276 in patients with gastric cancer by reverse transcription-digital polymerase chain reaction. Front Oncol 2022; 12:1042248. [PMID: 36620570 PMCID: PMC9816570 DOI: 10.3389/fonc.2022.1042248] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022] Open
Abstract
Background The role of circular RNAs (circRNAs) in the occurrence of gastric cancer is still unclear. Therefore, the diagnostic value and mechanisms underlying hsa_circ_0061276 in the occurrence of gastric cancer were explored. Methods Reverse transcription-droplet digital polymerase chain reaction was used to detect the copy number of hsa_circ_0061276 in plasma from healthy individuals, as well as from patients with gastric precancerous lesions or early-stage or advanced gastric cancer. Plasmids overexpressing or knocking down hsa_circ_0061276 expression were transfected into gastric cancer cells. The effects on the growth, migration, and cell cycle distribution of gastric cancer cells were then analyzed. Finally, miRanda and RNAhybrid were used to explore the binding sites between hsa_circ_0061276 and microRNAs (miRNAs). A double luciferase reporter gene assay was used to confirm the miRNA sponge effect. Results The results show that plasma hsa_circ_0061276 copy number showed a trend of a gradual decrease when comparing healthy controls to the early cancer group and advanced gastric cancer group. Overexpression of hsa_circ_0061276 inhibited the growth and migration of gastric cancer cells. Through bioinformatic analyses combined with cellular experiments, it was found that hsa_circ_0061276 inhibited the growth of gastric cancer by binding to hsa-miR-7705. Conclusion Hsa_circ_0061276 may be a new biomarker for gastric cancer. The tumor suppressor role of hsa_circ_0061276 on gastric cancer likely occurs through a sponge effect on miRNAs such as hsa-miR-7705.
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Affiliation(s)
- Yao Ruan
- Department of Gastrointestinal Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo, China,Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, School of Medicine, Ningbo University, Ningbo, China
| | - Zhe Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, School of Medicine, Ningbo University, Ningbo, China
| | - Yaoyao Xie
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, School of Medicine, Ningbo University, Ningbo, China
| | - Weiliang Sun
- Department of Gastrointestinal Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo, China,Institute of Gastrointestinal Tumor of Ningbo University, Ningbo, China
| | - Junming Guo
- Department of Gastrointestinal Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo, China,Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, School of Medicine, Ningbo University, Ningbo, China,Institute of Gastrointestinal Tumor of Ningbo University, Ningbo, China,*Correspondence: Junming Guo,
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15
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Li H, Xue S, Zhang X, Li F, Bei S, Feng L. CircRNA PVT1 modulated cell migration and invasion through Epithelial-Mesenchymal Transition (EMT) mediation in gastric cancer through miR-423-5p/Smad3 pathway. Regen Ther 2022; 21:25-33. [PMID: 35663842 PMCID: PMC9133701 DOI: 10.1016/j.reth.2022.02.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 01/05/2022] [Accepted: 02/19/2022] [Indexed: 02/07/2023] Open
Abstract
Background Gastric cancer (GC) progression is related with gene regulations. Objectives This study explored underlying regulatory axis of circRNA PVT1 (circPVT1) in GC. Methods GC cell lines were detected for circPVT1 expression with the normal mucous epithelial cell GES-1 as control. After regulation of circPVT1, miR-423-5p and SMAD3 expression through transfection, CCK8 evaluated the cell viability, Transwell measured the migratory and invasive capability of cells. Luciferase verified the paired bindings between miR-423-5p and CircPVT1 or SMAD3. The functions of CircPVT1/miR-423-5p/SMAD3 were evaluated using RT-PCR, CCK8, Transwell assays. Western blot analyzed EMT-related proteins and phosphorylation of Smad3 in GC cells. Immunofluorescence method was used to evaluate the EMT-related proteins as well. Results CircPVT1 displayed higher expression in GC cells and knockdown led to decrease in cell growth, invasion and migration. CircPVT1 was targeted by miR-423-5p as a ceRNA of SMAD3. miR-423-5p upregulation suppressed both cicRNA PVT1 and SMAD3 in GC cells. Decrease in SMAD3 expression suppressed CircPVT1 by releasing miR-423-5p in cells, inhibiting cell growth, invasion and migration and suppressing the EMT process. Conclusion CircPVT1 modulated cell growth, invasion and migration through EMT mediation in gastric cancer through miR-423-5p/Smad3 pathway.
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16
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Circular RNA circ-BNC2 (hsa_circ_0008732) inhibits the progression of ovarian cancer through microRNA-223-3p/ FBXW7 axis. J Ovarian Res 2022; 15:95. [PMID: 35965327 PMCID: PMC9377053 DOI: 10.1186/s13048-022-01025-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background Circular RNAs (circRNAs) are reported to be key regulators in the progression of human cancers. This work focuses on the function and molecular mechanism of circRNA-BNC2 (circ-BNC2) (also known as hsa_circ_0008732) in ovarian cancer (OC). Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect circ-BNC2, microRNA-223-3p (miR-223-3p) and F-box and WD repeat domain containing 7 (FBXW7) mRNA expressions in OC tissues and cells. Besides, cell counting kit 8 (CCK-8), transwell assay and cell cycle assays were executed to assess the proliferative, migrative, invasive abilities, and cell cycle progression of OC cells, respectively. Dual-luciferase reporter gene assay and RNA pull-down assay were used to validate the targeting relationships between miR-223-3p and circ-BNC2 or FBXW7. Western blot was adopted to determine FBXW7 protein levels in OC cells. Results Circ-BNC2 expression was downregulated in OC tissues and cell lines, which was associated with higher FIGO stage and lymph node metastasis of OC patients. Circ-BNC2 overexpression repressed the proliferation, migration, invasion of OC cells and induced cell cycle arrest, while silencing circ-BNC2 worked oppositely. Mechanistically, circ-BNC2 could upregulate FBXW7 expression in OC cells via sponging miR-223-3p. Conclusion Circ-BNC2 suppresses the progression of OC via regulating miR-223-3p / FBXW7 axis. Our findings provided potential biomarker for OC therapy.
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17
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Yan J, Shao Y, Lu H, Ye Q, Ye G, Guo J. Hsa_circ_0001020 Serves as a Potential Biomarker for Gastric Cancer Screening and Prognosis. Dig Dis Sci 2022; 67:3753-3762. [PMID: 34424459 DOI: 10.1007/s10620-021-07211-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 08/02/2021] [Indexed: 12/24/2022]
Abstract
Circular RNAs (circRNAs) are an intriguing class of RNAs with covalently closed-loop structures. With characteristics of high stability and disease-specific expression, circRNAs are emerging as ideal targets for cancer therapy. However, the screening utility and clinical value of circRNAs in gastric cancer (GC) remain largely elusive. We detected levels of hsa_circ_0001020 in cell lines and tissue and plasma samples and investigated its clinicopathological correlations. Kaplan-Meier survival curves and regression analyses were used to analyze its prognostic value. Receiver operating characteristic curves and biomarker combinations were examined to verify its screening value. Bioinformatics analysis was also performed to predict potential biological functions. Our tests found that hsa_circ_0001020 was significantly upregulated in GC cell lines, GC tissue samples, and even in plasma. High hsa_circ_0001020 expression levels in GC tissues were significantly associated with distal metastasis and blood carbohydrate antigen 19-9 (CA19-9). GC patients with high hsa_circ_0001020 had a lower overall survival and disease-free survival time than the low levels. Regression analysis suggested that the level of hsa_circ_0001020 expression was an independent prognostic factor for survival time. As a biomarker for GC, hsa_circ_0001020 showed a superior AUC, sensitivity, and specificity than carcinoembryonic antigen and CA19-9, and was suitable for combination with clinical tumor biomarkers. Bioinformatics analysis provided valuable clues for the possible oncogenic pathways of GC, such as the FoxO and p53 signaling pathways. In conclusion, our study found that hsa_circ_0001020 in GC could be a reliable biomarker to screen for GC and predict prognosis.
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Affiliation(s)
- Jianing Yan
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.,Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Haoxuan Lu
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China
| | - Qihua Ye
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China.
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.,Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
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18
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Dorostgou Z, Yadegar N, Dorostgou Z, Khorvash F, Vakili O. Novel insights into the role of circular RNAs in Parkinson disease: An emerging renaissance in the management of neurodegenerative diseases. J Neurosci Res 2022; 100:1775-1790. [PMID: 35642104 DOI: 10.1002/jnr.25094] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 05/11/2022] [Accepted: 05/15/2022] [Indexed: 11/06/2022]
Abstract
Parkinson's disease (PD), as a debilitating neurodegenerative disease, particularly affects the elderly population, and is clinically identified by resting tremor, rigidity, and bradykinesia. Pathophysiologically, PD is characterized by an early loss of dopaminergic neurons in the Substantia nigra pars compacta, accompanied by the extensive aggregation of alpha-synuclein (α-Syn) in the form of Lewy bodies. The onset of PD has been reported to be influenced by multiple biological molecules. In this context, circular RNAs (circRNAs), as tissue-specific noncoding RNAs with closed structures, have been recently demonstrated to involve in a set of PD's pathogenic processes. These RNA molecules can either up- or downregulate the expression of α-Syn, as well as moderating its accumulation through different regulatory mechanisms, in which targeting microRNAs (miRNAs) is considered the most common pathway. Since circRNAs have prominent structural and biological characteristics, they could also be considered as promising candidates for PD diagnosis and treatment. Unfortunately, PD has become a global health concern, and a large number of its pathogenic processes are still unclear; thus, it is crucial to elucidate the ambiguous aspects of PD pathophysiology to improve the efficiency of diagnostic and therapeutic strategies. In line with this fact, the current review aims to highlight the interplay between circRNAs and PD pathogenesis, and then discusses the diagnostic and therapeutic potential of circRNAs in PD progression. This study will thus be the first of its kind reviewing the relationship between circRNAs and PD.
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Affiliation(s)
- Zahra Dorostgou
- Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
| | - Negar Yadegar
- Department of Medical Laboratory Sciences, School of Paramedical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zeynab Dorostgou
- Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran
| | - Fariborz Khorvash
- Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Isfahan Neurosciences Research Center, Al-zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Qu D, Zou X, Liu Z. Propofol modulates glycolysis reprogramming of ovarian tumor via restraining circular RNA-zinc finger RNA-binding protein/microRNA-212-5p/superoxide dismutase 2 axis. Bioengineered 2022; 13:11881-11892. [PMID: 35543376 PMCID: PMC9275929 DOI: 10.1080/21655979.2022.2063649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Metabolic reprogramming refers to the transformation of the whole metabolic network covering glycolysis and mitochondrial metabolism, which is primarily manifested as the Warburg effect and mitochondrial metabolic reprogramming. Propofol (Pro) has been testified to suppress the malignancy of diversified human cancers. Nevertheless, its role in glycolysis is still uncertain. The purpose of this study was to determine whether Pro modulated glycolysis in ovarian cancer (OC) cells. Cell proliferation, apoptosis, migration, and invasion were tested via CCK-8, flow cytometry, and Transwell assays, respectively, and glucose intake, lactic acid, and ATP production were also determined. Pro restrained glycolysis via mediating the circular RNA-zinc finger RNA-binding protein (ZFR)/microRNA (miR)-212-5p/superoxide dismutase 2 (SOD2) axis. Additionally, Pro restrained cancer cell advancement via modulating circ-ZFR/miR-212-5p/SOD2 axis. In short, Pro restrained glycolysis via mediating the circ-ZFR/miR-212-5p/SOD2 axis. These results offered a better theoretical foundation for comprehending the molecular pathology of OC and provided a novel target for OC diagnosis and treatment.
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Affiliation(s)
- DongDong Qu
- Department of Anesthesiology, Jinan Maternal and Child Health Hospital, Jinan City, Shandong Province, China
| | - Xin Zou
- Department of Anesthesiology, Qingdao Women's and Children's Hospital, Qingdao City, Shandong Province, China
| | - ZhiLin Liu
- Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao City, Shandong Province, China
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Wei J, Li J, Geng D, Peng Y, Yang B, Wu H, Zhou Y. Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients. Front Surg 2022; 9:897583. [PMID: 35592126 PMCID: PMC9110967 DOI: 10.3389/fsurg.2022.897583] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/08/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients. Methods A total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended. Results The relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05). Conclusion The expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.
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21
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Salami R, Salami M, Mafi A, Vakili O, Asemi Z. Circular RNAs and glioblastoma multiforme: focus on molecular mechanisms. Cell Commun Signal 2022; 20:13. [PMID: 35090496 PMCID: PMC8796413 DOI: 10.1186/s12964-021-00809-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 11/25/2021] [Indexed: 12/12/2022] Open
Abstract
Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM. Video Abstract.
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Affiliation(s)
- Raziyeh Salami
- Department of Clinical Biochemistry, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Marziyeh Salami
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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22
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Zhu B, Ke L, Li P, Wang X, Yang L, Bai M, Chen M. CircACC1 Promotes NSCLC Proliferation via miR-29c-3p/MCL-1 Signaling Pathway. Front Genet 2022; 12:798587. [PMID: 35069696 PMCID: PMC8776987 DOI: 10.3389/fgene.2021.798587] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/25/2021] [Indexed: 12/03/2022] Open
Abstract
Non-small cell lung cancer remains the leading cause of cancer-related deaths worldwide with high morbidity and mortality. There is an urgent need to reveal new molecular mechanisms that contribute to NSCLC progression to facilitate drug development and to improve overall survival. Much attention has been paid to the role of circRNAs in NSCLC development. However, the knowledge of circRNAs in NSCLC is still limited, and need to be further explored. The dysregulation of circACC1 was evaluated by qRT-PCR in NSCLC samples and cell lines. The oncogenic role of circACC1 in NSCLC progression was analyzed by CCK8 and colony formation assays. The interaction between the circACC1 and miR-29c-3p, as well as MCL-1, was verified by qRT-PCR, Western blot, luciferase reporter assay, and RIP experiment. Elevated levels of circACC1 were found in NSCLC patients and were negatively correlated with OS. Ectopic expression of circACC1 promoted the capacity of cell growth and clonogenicity, while the inhibition of circACC1 decreased the proliferation and clonogenicity potential. Mechanism studies elucidated that circACC1 contributes to cell growth via directly binding to miR-29c-3p. Transfection of miR-29c-3p mimic blocked circACC1 mediated NSCLC cell proliferation. MCL-1 is a downstream target of miR-29c-3p in NSCLC cells. The circACC1/miR-29c-3p/MCL-1 axis is important in NSCLS proliferation.
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Affiliation(s)
- Bo Zhu
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lixia Ke
- Department of Medical Oncology, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, China
| | - Peixian Li
- Department of Medical Oncology, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, China
| | - Xin Wang
- Department of Medical Oncology, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, China
| | - Lan Yang
- Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Minghua Bai
- Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mailin Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Radiology of Department, Peking University Cancer Hospital and Institute, Beijing, China
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Tang SY, Zhou PJ, Meng Y, Zeng FR, Deng GT. Gastric cancer: An epigenetic view. World J Gastrointest Oncol 2022; 14:90-109. [PMID: 35116105 PMCID: PMC8790429 DOI: 10.4251/wjgo.v14.i1.90] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/17/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) poses a serious threat worldwide with unfavorable prognosis mainly due to late diagnosis and limited therapies. Therefore, precise molecular classification and search for potential targets are required for diagnosis and treatment, as GC is complicated and heterogeneous in nature. Accumulating evidence indicates that epigenetics plays a vital role in gastric carcinogenesis and progression, including histone modifications, DNA methylation and non-coding RNAs. Epigenetic biomarkers and drugs are currently under intensive evaluations to ensure efficient clinical utility in GC. In this review, key epigenetic alterations and related functions and mechanisms are summarized in GC. We focus on integration of existing epigenetic findings in GC for the bench-to-bedside translation of some pivotal epigenetic alterations into clinical practice and also describe the vacant field waiting for investigation.
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Affiliation(s)
- Si-Yuan Tang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Pei-Jun Zhou
- Cancer Research Institute, School of Basic Medicine Science, Central South University, School of Basic Medicine Science, Central South University 410008, Hunan Province, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Fu-Rong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Guang-Tong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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Xu P, Xu X, Wu X, Zhang L, Meng L, Chen Z, Han W, Yao J, Xu AM. CircTMC5 promotes gastric cancer progression and metastasis by targeting miR-361-3p/RABL6. Gastric Cancer 2022; 25:64-82. [PMID: 34296378 DOI: 10.1007/s10120-021-01220-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. METHODS CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). RESULTS CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CONCLUSIONS CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.
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Affiliation(s)
- Peng Xu
- Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230000, Anhui Province, China.,Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98, Nantong West Road, Yangzhou City, 225001, Jiangsu Province, China
| | - XiaoLan Xu
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
| | - Xiao Wu
- Department of Pathophysiology, Basic Medical College of Anhui Medical University, Anhui Provincial Key Laboratory of Pathophysiology, Hefei, 230022, China
| | - LiXiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui, Medical University, Hefei, 230022, China
| | - Lei Meng
- Department of General Surgery, The First Affiliated Hospital of Anhui, Medical University, Hefei, 230022, China
| | - ZhangMing Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui, Medical University, Hefei, 230022, China
| | - WenXiu Han
- Department of General Surgery, The First Affiliated Hospital of Anhui, Medical University, Hefei, 230022, China
| | - Jie Yao
- Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98, Nantong West Road, Yangzhou City, 225001, Jiangsu Province, China.
| | - AMan Xu
- Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230000, Anhui Province, China. .,Department of General Surgery, The First Affiliated Hospital of Anhui, Medical University, Hefei, 230022, China.
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25
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Wu F, Sun G, Zheng W, Tang W, Cheng Y, Wu L, Li X, Tao J, Ma S, Cao H. circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD-L1 through NF-κB pathway. J Clin Lab Anal 2021; 35:e24003. [PMID: 34676904 PMCID: PMC8649343 DOI: 10.1002/jcla.24003] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood. METHODS CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT-PCR, western blot, and other methods. RESULTS Among the thousands of circRNAs, 1238 circRNAs were significantly changed. As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa-circRNA3310-44, hsa_circ_0045746, hsa_circ_0016836, hsa-circRNA10899-9, hsa_circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circCORO1C activated the NF-κB signaling pathway, increased P65 phosphorylation and upregulation of c-Myc and COX-2, leading to increased PD-L1 expression. CONCLUSION CircCORO1C upregulates c-Myc and COX-2 through NF-κB signaling pathway, leading to the upregulation of PD-L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC.
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Affiliation(s)
- Fan Wu
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Guoqiang Sun
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Wubin Zheng
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Weiwei Tang
- Hepatobiliary/Liver Transplantation CenterKey Laboratory of Living Donor TransplantationChinese Academy of Medical SciencesThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Ye Cheng
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - LiangLiang Wu
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Xiao Li
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Jing Tao
- Department of General SurgeryNanjing Pukou HospitalNanjing Medical UniversityNanjingChina
| | - Shijie Ma
- Department of GastroenterologyThe Affiliated Huaian No.1 People's Hospital of Nanjing Medical UniversityHuaianChina
| | - Hongyong Cao
- Department of General SurgeryNanjing First HospitalNanjing Medical UniversityNanjingChina
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Zhang S, Sun J, Gu M, Wang G, Wang X. Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer. Cancer Med 2021; 10:8725-8740. [PMID: 34796685 PMCID: PMC8683543 DOI: 10.1002/cam4.4398] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 09/18/2021] [Accepted: 10/19/2021] [Indexed: 12/11/2022] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. According to the research of circular RNAs in the CRC field, compared with linear RNAs, circular RNAs are a special type of noncoding RNA that are covalently closed circular structures, which have no 5' cap structure and 3' polyA tail and are not affected by RNA exonuclease and actinomycin D. Biological functions Notably, circular RNAs have a high degree of stability and potential effect on gene regulation. Meanwhile, circular RNAs are involved in the sponge action of microRNAs and mediate protein translation and direct binding, alternative splicing, and histone modification. Relationships with CRC Studies have shown that circular RNAs are related to the proliferation, invasion, recurrence, metastasis, ferroptosis, apoptosis, and chemotherapy resistance of CRC. Conclusions This article provides a brief review based on the source, structural characteristics, mechanisms, biological functions of circular RNAs, and the relationships between CRC.
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Affiliation(s)
- Shunhao Zhang
- Graduate School of Nantong University, Nantong, China
| | - Jing Sun
- Graduate School of Nantong University, Nantong, China
| | - Minqi Gu
- Graduate School of Nantong University, Nantong, China
| | - Guihua Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Xudong Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
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Ma Y, Li Z, Ma D, Guo J, Sun W. Hsa_circ_0003195 as a biomarker for diagnosis and prognosis of gastric cancer. Int J Clin Oncol 2021; 27:354-361. [PMID: 34773528 DOI: 10.1007/s10147-021-02073-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/31/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Recent studies have shown that circular RNAs (circRNAs) are closely related to the occurrence and development of gastric cancer. In this paper, we analyzed the value of hsa_circ_0003195 in diagnosis and prognosis of gastric cancer. METHODS Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the level of hsa_circ_0003195 in 100 paired gastric cancer tissues and paracancerous tissues, 74 paired fasting plasma from gastric cancer patients before and 10 days after operation, and 74 fasting plasmas from healthy controls. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value. The survival analysis and Cox proportional-hazards model were used to evaluate the efficiency of hsa_circ_0003195 in predicting overall survival (OS) in patients with gastric cancer. RESULTS The expression of hsa_circ_0003195 was down-regulated in gastric cancer tissues and plasma from patients with gastric cancer. The expression level of hsa_circ_0003195 was correlated with differentiation, TNM stages, lymphatic metastasis, and distal metastasis. The area under the ROC curve (AUC) of tissue and plasma hsa_circ_0003195 was 0.684 and 0.695, respectively. The plasma hsa_circ_0003195 can be used as predictors of survival of patients with gastric cancer. CONCLUSION Hsa_circ_0003195 may be a new diagnostic and prognostic marker of gastric cancer.
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Affiliation(s)
- Yibo Ma
- The Affiliated People's Hospital, Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Zhe Li
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Dongnan Ma
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Junming Guo
- The Affiliated People's Hospital, Ningbo University, Ningbo, China. .,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China.
| | - Weiliang Sun
- The Affiliated People's Hospital, Ningbo University, Ningbo, China.
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Yao Q, He YL, Wang N, Dong SS, Tu He Ta Mi Shi ME, Feng X, Chen H, Pang LJ, Zou H, Zhou WH, Li F, Qi Y. Identification of Potential Genomic Alterations and the circRNA-miRNA-mRNA Regulatory Network in Primary and Recurrent Synovial Sarcomas. Front Mol Biosci 2021; 8:707151. [PMID: 34485383 PMCID: PMC8414803 DOI: 10.3389/fmolb.2021.707151] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 07/28/2021] [Indexed: 12/29/2022] Open
Abstract
Introduction: Synovial sarcoma (SS) is one of the most invasive soft tissue sarcomas, prone to recurrence and metastasis, and the efficacy of surgical treatment and chemotherapy for SS remains poor. Therefore, the diagnosis and treatment of SS remain a significant challenge. This study aimed to analyze the mutated genes of primary SS (PSS) and recurrent SS (RSS), discover whether these sarcomas exhibit some potential mutated genes, and then predict associated microRNAs (miRNA) and circular RNAs (circRNA) by analyzing the mutated genes. We focused on the regulation mechanism of the circRNA-miRNA-mutated hub gene in PSS and RSS. Methods: We performed a comprehensive genomic analysis of four pairs of formalin-fixed paraffin-embedded samples of PSS and RSS, using Illumina human exon microarrays. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) function, and pathway enrichment of the mutated genes were analyzed, and the protein-protein interaction (PPI) network was forecast using String software 11.0. The hub genes were then obtained using the Molecular Complex Detection (MCODE) plug-in for Cytoscape 3.7.2 and were used to analyze overall survival (OS) using the Gene Expression Profiling Interactive Analysis (GEPIA) database. The corresponding miRNAs were obtained from the miRDB 5.0 and TargetScan 7.2 databases. The corresponding circRNAs of the hub genes were found through the miRNAs from these databases: Circbank, CircInteractome, and StarBase v2.0. Thereafter we set up a competing endogenous RNA (ceRNA) network with circRNA-miRNA and miRNA-messenger RNA (mRNA) pairs. Results: Using the chi-squared test, 391 mutated genes were screened using a significance level of p-values < 0.01 from the four pairs of PSS and RSS samples. A GO pathway analysis of 391 mutated genes demonstrated that differential expression mRNAs (DEmRNAs) might be bound up with the “positive regulation of neurogenesis,” “cell growth,” “axon part,” “cell−substrate junction,” or “protein phosphatase binding” of SS. The PPI network was constructed using 391 mutated genes, and 53 hub genes were identified (p < 0.05). Eight variant hub genes were discovered to be statistically significant using the OS analysis (p < 0.05). The circRNA-miRNA-mRNA (ceRNA) network was constructed, and it identified two circRNAs (hsa_circ_0070557 and hsa_circ_0070558), 10 miRNAs (hsa-let-7a-3p, hsa-let-7b-3p, hsa-let-7f-1-3p, hsa-let-7f-2-3p, hsa-mir-1244, hsa-mir-1197, hsa-mir-124-3p, hsa-mir-1249-5p, hsa-mir-1253, and hsa-mir-1271-5p) and five hub genes (CENPE, ENPP3, GPR18, MDC1, and PLOD2). Conclusion: This study screened novel biological markers and investigated the differentiated circRNA-miRNA-mutated hub gene axis, which may play a pivotal role in the nosogenesis of PSS and RSS. Some circRNAs may be deemed new diagnostic or therapeutic targets that could be conducive to the future clinical treatment of SS.
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Affiliation(s)
- Qing Yao
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Yong-Lai He
- Department of Pathology, Certral People's Hospital of Zhanjiang and Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, China
| | - Ning Wang
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Shuang-Shuang Dong
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Mei Er Tu He Ta Mi Shi
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Xiao Feng
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Hao Chen
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Li-Juan Pang
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Hong Zou
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China
| | - Wen-Hu Zhou
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Feng Li
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China.,Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yan Qi
- Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, China.,Department of Pathology, Certral People's Hospital of Zhanjiang and Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, China
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Chen X, Tang Y, Yan J, Li L, Jiang L, Chen Y. Circ_0062270 upregulates EPHA2 to facilitate melanoma progression via sponging miR-331-3p. J Dermatol Sci 2021; 103:176-182. [PMID: 34454812 DOI: 10.1016/j.jdermsci.2021.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND Circular RNA (circRNA) has been confirmed to play a vital role in melanoma progression. OBJECTIVE The regulatory function of circ_0062270, a novel circRNA, in melanoma progression is unclear. METHODS Relative expression levels of circ_0062270 and microRNA (miR)-331-3p were determined using qRT-PCR. Cell counting kit 8 assay, EdU staining and flow cytometry were used to measure cell proliferation, cell cycle distribution and apoptosis. The protein levels of proliferation, apoptosis and metastasis-related markers, as well as EPH receptor A2 (EPHA2), were tested using western blot analysis. Besides, cell migration and invasion were evaluated using transwell assay. Meanwhile, the interaction between miR-331-3p and circ_0062270 or EPHA2 was confirmed by dual-luciferase reporter assay or RIP assay. Additionally, tumor xenograft models were constructed to investigate the function of circ_0062270 on melanoma tumor growth in vivo. RESULTS The expression of circ_0062270 was increased in melanoma tissues and cells. Knockdown of circ_0062270 inhibited proliferation, promoted apoptosis, and repressed metastasis in melanoma. Moreover, circ_0062270 could serve as miR-331-3p sponge, and miR-331-3p could target EPHA2. Furthermore, miR-331-3p inhibitor and EPHA2 overexpression reversed the inhibitory effect of circ_0062270 silencing on melanoma progression. In addition, silenced circ_0062270 also could inhibit melanoma tumor growth in vivo. CONCLUSION Circ_0062270 accelerated the progression of melanoma through regulating the miR-331-3p/EPHA2 axis, suggesting that circ_0062270 might be a novel potential therapeutic target for melanoma.
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Affiliation(s)
- Xiaogang Chen
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China
| | - Yichen Tang
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China
| | - Jianna Yan
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China
| | - Liang Li
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China
| | - Long Jiang
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China
| | - Yuchong Chen
- Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China.
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Gao Y, Li G, Fan S, Wang Y, Wei H, Li M, Li X. Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox-LDL-induced endothelial dysfunction in atherosclerosis by functioning as a miR-876-3p sponge. Clin Exp Pharmacol Physiol 2021; 48:1137-1149. [PMID: 33844344 DOI: 10.1111/1440-1681.13504] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 12/23/2022]
Abstract
Circular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK-8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell-cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR-876-3p, CCND2 and SUCNR1 were assayed by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR-876-3p axis on cell proliferation, migration and tube formation. Oxidized low-density lipoprotein inhibited cell viability and cell-cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR-876-3p was upregulated in AS patients and ox-LDL-treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox-LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR-876-3p and miR-876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR-876-3p. Meanwhile, miR-876-3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR-876-3p also alleviated the ox-LDL-induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR-876-3p. The protective effects of circ_0093887 on HAECs from ox-LDL were also alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox-LDL-induced inflammatory and apoptotic damages by targeting the miR-876-3p/CCND2 or miR-876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.
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Affiliation(s)
- Yanhui Gao
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Guangnan Li
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shasha Fan
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yu Wang
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hong Wei
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mingyang Li
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xueqi Li
- Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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Zhang J, Zha W, Qian C, Ding A, Mao Z. Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis. Biochem Genet 2021; 60:558-575. [PMID: 34313883 DOI: 10.1007/s10528-021-10110-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 07/06/2021] [Indexed: 12/24/2022]
Abstract
Resistance to cisplatin (CDDP) remains a major challenge for the treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been implicated in the development of CDDP resistance of GC. However, the precise actions of circ_0001017 in CDDP resistance of GC remain to be elucidated. The levels of circ_0001017, microRNA (miR)-543 and PH-domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze the protein levels of Vimentin, N-cadherin, E-cadherin, and PHLPP2. Ribonuclease R (RNase R) assay was applied to evaluate the stability of circ_0001017. Cell viability and proliferation, colony formation ability, cell cycle distribution and apoptosis, and migration and invasion were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Direct relationship between miR-543 and circ_0001017 or PHLPP2 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assay was used to assess the function of circ_0001017 in vivo. Low expression of circ_0001017 was associated with CDDP resistance of GC. Enforced expression of circ_0001017 impeded growth, metastasis, and enhanced apoptosis of HGC-27/R and AGS/R cells and sensitized them to CDDP in vitro. Circ_0001017 targeted miR-543, and circ_0001017 regulated CDDP-resistant cell behaviors and CDDP sensitivity by suppressing miR-543. PHLPP2 was a direct target of miR-543, and circ_0001017 controlled PHLPP2 expression through miR-543. Moreover, miR-543 knockdown-mediated promotion of PHLPP2 impacted CDDP-resistant cell behaviors and CDDP sensitivity in vitro. Additionally, elevated expression of circ_0001017 hindered growth of HGC-27/R cells and sensitized them to CDDP in vivo. Our findings demonstrated that enforced expression of circ_0001017 suppressed malignant behaviors and enhanced CDDP sensitivity of CDDP-resistant GC cells at least partially by the miR-543/PHLPP2 axis.
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Affiliation(s)
- Jianmin Zhang
- Department of General Surgery, First Affiliated Hospital of Soochow University, No.899 Pinghai Road, Suzhou City, 215000, Jiangsu Province, China.,Departments of General Surgery, Yancheng City No.1 People's Hospital, Yancheng City, Jiangsu Province, China
| | - Wenzhang Zha
- Departments of General Surgery, Yancheng City No.1 People's Hospital, Yancheng City, Jiangsu Province, China
| | - Changchun Qian
- Departments of General Surgery, Yancheng City No.1 People's Hospital, Yancheng City, Jiangsu Province, China
| | - Aixing Ding
- Departments of General Surgery, Yancheng City No.1 People's Hospital, Yancheng City, Jiangsu Province, China
| | - Zhongqi Mao
- Department of General Surgery, First Affiliated Hospital of Soochow University, No.899 Pinghai Road, Suzhou City, 215000, Jiangsu Province, China.
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Zheng Q, Zhang J, Zhang T, Liu Y, Du X, Dai X, Gu D. Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation. J Transl Med 2021; 19:314. [PMID: 34284793 PMCID: PMC8290540 DOI: 10.1186/s12967-021-02953-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/19/2021] [Indexed: 01/04/2023] Open
Abstract
Background Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. Methods Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. Results Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. Conclusion These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02953-9.
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Affiliation(s)
- Qingling Zheng
- Department of Obstetrics and Gynecology, School of Medicine, Huzhou University, Huzhou, 313000, People's Republic of China
| | - Jin Zhang
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Ting Zhang
- Department of Pathology, School of Medicine, Huzhou University, Huzhou, 313000, People's Republic of China
| | - Yanxiang Liu
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Xiuluan Du
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Xin Dai
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Donghua Gu
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China.
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Yang B, Li L, Tong G, Zeng Z, Tan J, Su Z, Liu Z, Lin J, Gao W, Chen J, Zeng S, Wu G, Li L, Zhu S, Liu Q, Lin L. Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:235. [PMID: 34271943 PMCID: PMC8283840 DOI: 10.1186/s13046-021-02027-0] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/23/2021] [Indexed: 01/01/2023]
Abstract
Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422. Results We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells. Conclusions Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02027-0.
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Affiliation(s)
- Bingsheng Yang
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Lutao Li
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Ge Tong
- Department of Medical Ultrasonics, Guangdong Province Key Laboratory of Hepatology Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Zhirui Zeng
- Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, 550009, China
| | - Jianye Tan
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Zexin Su
- Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Zhengwei Liu
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Jiezhao Lin
- Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Wenwen Gao
- Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Jianping Chen
- Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Sisi Zeng
- Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Guofeng Wu
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Lin Li
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Shuang Zhu
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Qiuzhen Liu
- Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
| | - Lijun Lin
- Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
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Bella F, Campo S. Long non-coding RNAs and their involvement in bipolar disorders. Gene 2021; 796-797:145803. [PMID: 34175394 DOI: 10.1016/j.gene.2021.145803] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/22/2021] [Indexed: 01/22/2023]
Abstract
Non-coding RNAs (nc-RNAs) can be defined as RNA molecules that are not translated into proteins. Although the functional meaning of many nc-RNAs remains still to be verified, several of these molecules have a clear biological importance, which goes from translation of mRNAs to DNA replication. Indeed, regulatory nc-RNAs can be classified into two groups: short non-coding RNAs (sncRNAs) and long-non coding RNAs (lncRNAs). In the last years, lncRNAs have gained increasing importance in the study of gene regulation, helping authors understand the molecular mechanisms underlying cellular physiology and pathology. LncRNAs are greater than 200 bp and accumulate in nucleus, cytoplasm and exosomes with high tissue specificity, acting in cis or in trans in order to exert enhancer or silencer modulation on gene expression. Such regulatory features, which are widespread in human cells and tissues, can be disrupted in several morbid states. Recent evidences may suggest a disruption of lncRNAs in bipolar disorders, a cluster of severe, chronic and disabling psychiatric diseases, which are characterized by major depressive states cyclically alternating with manic episodes. Here, the authors reviewed genes, classification, biogenesis, structures, functions and databases regarding lncRNAs, and also focused on bipolar disorders, in which some lncRNAs, especially those involved in inflammation and neuronal development, has reported to be dysregulated.
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Affiliation(s)
- Fabrizio Bella
- Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, via Consolare Valeria, 1, Messina 98125 Italy
| | - Salvatore Campo
- Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, via Consolare Valeria, 1, Messina 98125 Italy.
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Yao L, Xie Y. Down-regulation of hsa_circ_0006470 predicts tumor invasion: A new biomarker of gastric cancer. J Clin Lab Anal 2021; 35:e23879. [PMID: 34165822 PMCID: PMC8373341 DOI: 10.1002/jcla.23879] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 05/28/2021] [Accepted: 06/06/2021] [Indexed: 12/14/2022] Open
Abstract
Background Gastric cancer (GC) is a common cancer. Circular RNAs (circRNAs) regulate the pathogenesis of GC. This study aims to explore its potential as a GC biomarker. Methods The expression of hsa_circ_0006470 in GC tissues and GC cell lines was measured by quantitative reverse transcription‐polymerase chain reaction. The diagnostic value of hsa_circ_0006470 was estimated by the receiver operating characteristic (ROC) curve. Results Compared with adjacent normal tissues, the expression of hsa_circ_0006470 in GC tissues was significantly lower. The expression levels of hsa_circ_0006470 in different TNM stages and different invasion degrees were significantly different. The area under the ROC curve was 0.783, with sensitivity and specificity 0.725 and 0.750, respectively. Conclusions Hsa_circ_0006470 has a high value as a diagnostic biomarker for GC.
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Affiliation(s)
- Lipeng Yao
- Ningbo College of Health Sciences, Ningbo, Zhejiang, China.,Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Yaoyao Xie
- Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang, China
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36
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Lu Y, Li Z, Lin C, Zhang J, Shen Z. Translation role of circRNAs in cancers. J Clin Lab Anal 2021; 35:e23866. [PMID: 34097315 PMCID: PMC8275004 DOI: 10.1002/jcla.23866] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/24/2021] [Accepted: 05/24/2021] [Indexed: 12/24/2022] Open
Abstract
Circular RNAs (circRNAs) constitute a class of covalently closed RNA molecules. With the continuous advancement of high‐throughput sequencing technology and bioinformatics tools, many circRNAs have been identified in various human tissues and cell lines. Notably, recent studies have indicated that some circRNAs have translational functions. Internal ribosome entry sites and the N6‐methyladenosine modification mediate cap‐independent translation. This review describes these two translation mechanisms and verification methods at the molecular level. Databases (including ORF Finder, Pfam, BLASTp, CircRNADb, CircBase, CircPro, CircCode, IRESite, IRESbase) were used to analyze whether circRNAs have the structural characteristic of translation. CircRNA minigene reporter system containing green fluorescent protein (GFP) confirmed the translation potential of circRNAs. Also, we briefly summarize the roles of proteins/peptides encoded by circRNAs (circFBXW7, circFNDC3B, circLgr4, circPPP1R12A, circMAPK1, circβ‐catenin, circGprc5a, circ‐SHPRH, circPINTexon2, circAKT3) that have been verified thus far in human cancers (triple‐negative breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, bladder cancer, glioblastoma). Those findings suggest circRNAs have a great implication in translation of the human genome.
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Affiliation(s)
- Yaqin Lu
- Ningbo University School of MedicineNingboChina
| | - Zhe Li
- Ningbo University School of MedicineNingboChina
| | - Chen Lin
- Ningbo University School of MedicineNingboChina
| | - Jian Zhang
- Li Huili Hospital Affiliated to Ningbo University SchoolNingboChina
| | - Zhisen Shen
- Li Huili Hospital Affiliated to Ningbo University SchoolNingboChina
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Xia F, Zhang Z, Li X. Emerging Roles of Circular RNAs in Thyroid Cancer. Front Cell Dev Biol 2021; 9:636838. [PMID: 33981702 PMCID: PMC8107370 DOI: 10.3389/fcell.2021.636838] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/02/2021] [Indexed: 12/26/2022] Open
Abstract
Thyroid cancer (TC) has the highest incidence among endocrine malignancies. Thus, it is essential to achieve a deep understanding of various mechanisms of development and progression of TC. circRNAs are recognized by multiple studies as being dysregulated in TC. Accumulating evidences have revealed that circRNAs serve as regulatory molecules involved in various biological processes in TC, including cell proliferation, apoptosis, invasion/migration, metabolism, and chemoresistance. Furthermore, circRNA can also serve as an effective tool in TC researches of diagnosis, prognosis, and treatments. Thus, this review is to outline the characteristics of circRNAs, generalize their categories and functions, and highlight the expression of circRNAs in TC. Meanwhile, we are expecting to achieve a comprehensive understanding of new therapies based on circRNAs in treating or preventing TC.
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Affiliation(s)
- Fada Xia
- Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Zeyu Zhang
- Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Xinying Li
- Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, China
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38
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Gao H, Xu J, Qiao F, Xue L. Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis. Onco Targets Ther 2021; 14:2773-2787. [PMID: 33907420 PMCID: PMC8068497 DOI: 10.2147/ott.s281238] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/26/2021] [Indexed: 12/21/2022] Open
Abstract
Background Circular RNAs (circRNAs) have been disclosed to exert important roles in human cancers, including gastric cancer (GC). CircRNA hsa_circ_0000144 was identified as an oncogene in GC development. The aim of our study was to explore the role of hsa_circ_0000144 in oxaliplatin (OXA) resistance of GC. Methods Expression levels of hsa_circ_0000144, microRNA-502-5p (miR-502-5p) and A disintegrin and metalloproteinase 9 (ADAM9) were examined by quantitative real-time PCR (RT-qPCR) or Western blot assay. The OXA resistance of GC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed to assess the colony formation capacity. Cell apoptosis was determined by flow cytometry and caspase 3 activity. And cell migration and invasion were detected by Transwell assay. Target association between miR-502-5p and hsa_circ_0000144 or ADAM9 was demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Moreover, role of hsa_circ_0000144 in vivo was analyzed by xenograft tumor assay. Results Hsa_circ_0000144 and ADAM9 were highly expressed, while miR-502-5p was downregulated in OXA-resistant GC tissues and cells. Depletion of hsa_circ_0000144 could inhibit OXA resistance, proliferation and metastasis in OXA-resistant GC cells, which was attenuated by miR-502-5p inhibition. Hsa_circ_0000144 sponged miR-502-5p to positively regulate ADAM9 expression. MiR-502-5p suppressed OXA resistance, proliferation and metastasis in OXA-resistant GC cells by targeting ADAM9. Hsa_circ_0000144 knockdown could hamper tumor growth in vivo. Conclusion Hsa_circ_0000144 exerted inhibitory effects on OXA resistance, proliferation and metastasis of OXA-resistant GC cells by regulating miR-502-5p/ADAM9 axis, at least in part.
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Affiliation(s)
- Haifeng Gao
- Department of Clinical Laboratory, Baoji Central Hospital, Baoji City, 721008, Shaanxi Province, People's Republic of China
| | - Jiajia Xu
- Department of Organic Chemistry and Pharmaceutical Chemistry, Pharmaceutical College of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Fen Qiao
- Department of Pediatrics, Baoji Central Hospital, Baoji City, Shaanxi Province, People's Republic of China
| | - Liangjun Xue
- Department of Radiotherapy, Yijishan Hospital of Wannan Medical College, Wuhu City, Anhui Province, 241001, People's Republic of China
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Sun W, Zhang H, Duan W, Zhu H, Gu C. Tumor suppressor role of hsa_circ_0035445 in gastric cancer. J Clin Lab Anal 2021; 35:e23727. [PMID: 33830559 PMCID: PMC8183929 DOI: 10.1002/jcla.23727] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/09/2021] [Accepted: 01/21/2021] [Indexed: 12/24/2022] Open
Abstract
Circular RNAs (circRNAs) are closely related to the occurrence and development of cancers. However, the roles of circRNAs in gastric cancer are largely unknown. Total 104 pairs of gastric cancer tissues and non‐cancer tissues, fasting plasma of 42 healthy people and 42 gastric cancer patients’ one day before operation and 10 days after operation were collected. Quantitative reverse transcription‐polymerase chain reaction was used to detect the expression level of hsa_circ_0035445. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to analyze its diagnostic value. Small interfering RNA and overexpression vector were used to downregulate and upregulate the expression of hsa_circ_0035445, respectively. Cell Counting Kit‐8 and colony formation assays were used to detect the proliferation ability. Trans‐well assay and scratch assay were used to detect the migration ability. Finally, flow cytometry was used to detect the changes of cell cycle distribution and apoptosis. Hsa_circ_0035445 was lowly expressed in gastric cancer tissues, plasma of gastric cancer patients, and gastric cancer cells. The expression level of hsa_circ_0035445 in gastric cancer tissues was relationship with tumor size and distant metastasis. The AUC of hsa_circ_0035445 in tissues and plasma was 0.68 and 0.86, respectively. Upregulation of hsa_circ_0035445 suppressed the proliferation and migration, promoted apoptosis, and blocked cells at G0/G1 phase. Downregulation of hsa_circ_0035445 promoted the proliferation and migration, suppressed apoptosis, and blocked cells at S phase. In conclusion, hsa_circ_0035445 may become a new target for the treatment of gastric cancer.
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Affiliation(s)
- Weiliang Sun
- The Affiliated People's Hospital, Ningbo University, Ningbo, China
| | - Haiyan Zhang
- The Affiliated People's Hospital, Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China
| | - Wenbiao Duan
- The Affiliated People's Hospital, Ningbo University, Ningbo, China
| | - Hui Zhu
- The Affiliated People's Hospital, Ningbo University, Ningbo, China
| | - Chijiang Gu
- The Affiliated People's Hospital, Ningbo University, Ningbo, China
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Tao X, Shao Y, Yan J, Yang L, Ye Q, Wang Q, Lu R, Guo J. Biological roles and potential clinical values of circular RNAs in gastrointestinal malignancies. Cancer Biol Med 2021; 18:j.issn.2095-3941.2020.0348. [PMID: 33710802 PMCID: PMC8185857 DOI: 10.20892/j.issn.2095-3941.2020.0348] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 11/19/2020] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs), a class of endogenous RNA molecules, are produced by alternative splicing of precursor RNA and are covalently linked at the 5' and 3' ends. Recent studies have revealed that dysregulated circRNAs are closely related to the occurrence and progression of gastrointestinal malignancies. Accumulating evidence indicates that circRNAs, including circPVT1, circLARP4, circ-SFMBT2, cir-ITCH, circRNA_100782, circ_100395, circ-DONSON, hsa_circ_0001368, circNRIP1, circFAT1(e2), circCCDC66, circSMARCA5, circ-ZNF652, and circ_0030235 play important roles in the proliferation, differentiation, invasion, and metastasis of cancer cells through a variety of mechanisms, such as acting as microRNA sponges, interacting with RNA-binding proteins, regulating gene transcription and alternative splicing, and being translated into proteins. With the characteristics of high abundance, high stability, extensive functions, and certain tissue-, time- and disease-specific expressions, circRNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.
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Affiliation(s)
- Xueping Tao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Yongfu Shao
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Jianing Yan
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Liyang Yang
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Qihua Ye
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Qingling Wang
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Rongdan Lu
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
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He X, Xu T, Hu W, Tan Y, Wang D, Wang Y, Zhao C, Yi Y, Xiong M, Lv W, Wu M, Li X, Wu Y, Zhang Q. Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer. Front Cell Dev Biol 2021; 9:647736. [PMID: 33777954 PMCID: PMC7991790 DOI: 10.3389/fcell.2021.647736] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.
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Affiliation(s)
- Xiao He
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Xu
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weijie Hu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yufang Tan
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dawei Wang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yichen Wang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chongru Zhao
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Yi
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingchen Xiong
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenchang Lv
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Wu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xingrui Li
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiping Wu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Zhang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Liu Z, Wang R, Zhu G. Circ_0035483 Functions as a Tumor Promoter in Renal Cell Carcinoma via the miR-31-5p-Mediated HMGA1 Upregulation. Cancer Manag Res 2021; 13:693-706. [PMID: 33531839 PMCID: PMC7846871 DOI: 10.2147/cmar.s282806] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/15/2020] [Indexed: 12/17/2022] Open
Abstract
Background Renal cell carcinoma (RCC) that originates from the proximal renal tubules is the most common cancer of the human kidney. Increasing circRNA/miRNA/mRNA networks have been found in RCC regulation. This study will explore the regulatory relation of circular RNA (circRNA) circ_0035483, microRNA-31-5p (miR-31-5p) and high mobility group A1 (HMGA1). Methods The levels of circ_0035483, miR-31-5p and HMGA1 were measured by real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation was determined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were assessed by transwell assay. HMGA1 and epithelial–mesenchymal transition (EMT)-related protein levels were quantified using Western blot. Glycolytic metabolism was evaluated by glucose consumption and lactate production. The interaction between targets was confirmed via dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo experiment was performed through the establishment of xenograft models in mice. Results Circ_0035483 expression was upregulated in RCC tissues and cells. The inhibitory effects on RCC cell proliferation, migration, invasion, EMT and glycolysis were induced after circ_0035483 was downregulated. MiR-31-5p was identified as a target of circ_0035483 and miR-31-5p upregulation was related to the function of circ_0035483 knockdown in RCC cells. Additionally, miR-31-5p targeted HMGA1 and inhibited the malignant behaviors of RCC cells by negatively regulating HMGA1. Moreover, HMGA1 expression was regulated by circ_0035483 via targeting miR-31-5p. Circ_0035483 also affected tumor growth in vivo by relying on the miR-31-5p/HMGA1 axis. Conclusion These findings clarified that the tumor-promoting function of circ_0035483 in RCC was partly achieved by regulating the miR-31-5p/HMGA1 axis.
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Affiliation(s)
- Zheng Liu
- Department of Traditional Chinese Medicine and Acupuncture, Central Hospital of Baoji, Baoji City, Shaanxi Province, People's Republic of China
| | - Ronghai Wang
- Department of Urology, Linzi District People's Hospital, Zibo City, Shandong Province, People's Republic of China
| | - Guangze Zhu
- Department of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun City, Jilin Province, People's Republic of China
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Kalifu B, Maitiseyiti A, Ge X, Chen X, Meng Y. Expression profile of circular RNAs in cystic echinococcosis pericystic tissue. J Clin Lab Anal 2021; 35:e23687. [PMID: 33411343 PMCID: PMC7957996 DOI: 10.1002/jcla.23687] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/23/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023] Open
Abstract
Objective The aim of the present study was to investigate the expression profiles of circular RNAs (circRNAs) in the pericystic tissue of patients with cystic echinococcosis (CE). Patients and methods CircRNA expression profiles were obtained by circRNA microarray of four matched pairs of pericystic tissues affected by CE and adjacent normal liver tissues. qRT‐PCR was used to validate the differential expression of some circRNAs identified by the microarray analysis. The potential functions of the differentially expressed circRNAs in the CE pericystic tissues were predicted by bioinformatic analysis. Results Compared with the adjacent normal liver tissues, 177 circRNAs were upregulated and 166 circRNAs were downregulated in CE pericystic tissues based on a ≥2.0‐fold change. The top 10 upregulated circRNAs were hsa_circRNA_001654,hsa_circRNA_103361,hsa_circRNA_001490,hsa_circRNA_104310,hsa_circRNA_100395,hsa_circRNA_102485,hsa_circRNA_001459,hsa_circRNA_104193,hsa_circRNA_400043, and hsa_circRNA_006773; The top 10 downregulated circRNAs were hsa_circRNA_400633,hsa_circRNA_404974,hsa_circRNA_068482 ,hsa_circRNA_100974,hsa_circRNA_049637,hsa_circRNA_404798,hsa_circRNA_400064,hsa_circRNA_004045,hsa_circRNA_101379, and hsa_circRNA_016771;The circRNA‐seq results for 15 selected differentially expressed circRNAs were validated by qRT‐PCR. The qRT‐PCR analysis showed that hsa_circRNA_006773, hsa_circRNA_049637, hsa_circRNA_104349, and hsa_circRNA_406281 were differentially expressed in CE pericystic tissues when compared with their expression in the adjacent normal liver tissues. Interestingly, 319 miRNAs and 52 mRNAs were predicted to be adsorbed by these four differentially expressed circRNAs. Gene Ontology analysis revealed that these circRNAs may be involved in the response to organic cyclic compounds and endogenous stimuli and in cellular organismal processes. Conclusion Differential expression of circRNAs may be associated with the development and progression of CE, and these circRNAs might be useful as biomarkers for prognosis prediction and as treatment targets.
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Affiliation(s)
- Baheti Kalifu
- Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.,Department of Vascular and Hepatobilliry Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Abulaihaiti Maitiseyiti
- Department of Vascular and Hepatobilliry Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xiaohu Ge
- Department of Vascular and Hepatobilliry Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xiong Chen
- Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yuan Meng
- Department of Vascular and Hepatobilliry Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
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Li F, Wen N, Hu Q, Yang D, Yue C, Li Z, Lu H. Circular RNA Circ_0001017 Acts as ceRNA Adsorbing miR-197-3p to Regulate PNLIP Signaling and Affect the Proliferation, Apoptosis and Glycolysis of Pancreatic Ductal Adenocarcinoma Cells. J HARD TISSUE BIOL 2021. [DOI: 10.2485/jhtb.30.239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Fang Li
- Operating Room of Anesthesia Surgery Center, West China Hospital, Sichuan University
| | - Na Wen
- West China School of Nursing, Sichuan University
| | - Qian Hu
- West China School of Nursing, Sichuan University
| | - Dujiang Yang
- Institute of Digestive Surgery, West China Hospital, Sichuan University
| | - Chao Yue
- Department of Pancreatic Surgery, West China Hospital, Sichuan University
| | - Zhenlu Li
- Department of Pancreatic Surgery, West China Hospital, Sichuan University
| | - Huimin Lu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University
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Shen Y, Yu X, Ruan Y, Li Z, Xie Y, Yan Z, Guo J. Global profile of tRNA-derived small RNAs in gastric cancer patient plasma and identification of tRF-33-P4R8YP9LON4VDP as a new tumor suppressor. Int J Med Sci 2021; 18:1570-1579. [PMID: 33746573 PMCID: PMC7976566 DOI: 10.7150/ijms.53220] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 01/17/2021] [Indexed: 12/14/2022] Open
Abstract
Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been found to play important roles in the occurrence and development of cancers. However, the tsRNA profile in gastric cancer is unknown. In this study, we aimed to identify the global tsRNA profile in plasma from gastric cancer patients and elucidate the role of tRF-33-P4R8YP9LON4VDP in gastric cancer. Differentially expressed tsRNAs in the plasma of gastric cancer patients and healthy controls were investigated using RNA sequencing. The expression levels of tRF-33-P4R8YP9LON4VDP in the plasma of gastric cancer patients, healthy controls and gastric cancer cell lines were first detected by quantitative reverse transcription-polymerase chain reaction. The effects of tRF-33-P4R8YP9LON4VDP overexpression or downregulation in gastric cancer cells on proliferation, migration, apoptosis, and cell cycle were analyzed using the Cell Counting Kit-8, scratch assay, Transwell assay, and flow cytometry, respectively. There were 21 upregulated and 46 downregulated tsRNAs found in plasma from gastric cancer patients. The significantly upregulated tsRNAs included tRF-18-S3M83004, tRF-31-PNR8YP9LON4VD, tRF-19-3L7L73JD, tRF-33-P4R8YP9LON4VDP, tRF-31-PER8YP9LON4VD, tRF-18-MBQ4NKDJ, and tRF-31-PIR8YP9LON4VD. The significantly downregulated tsRNAs included tRF-41-YDLBRY73W0K5KKOVD, tRF-18-07QSNHD2, tRF-28-86J8WPMN1E0J, tRF-29-86V8WPMN1EJ3, tRF-31-6978WPRLXN4VE, tRF-30-MIF91SS2P46I, tRF-26-MI7O3B1NR8E, tRF-30-RRJ89O9NF5W8, tRF-26-XIP2801MK8E, and tRF-35-V0J8O9YEKPRS93, In vitro studies showed that tRF-33-P4R8YP9LON4VDP inhibited proliferation of gastric cancer cells. In conclusion, tsRNAs such as tRF-33-P4R8YP9LON4VDP could serve as a novel diagnostic biomarker and target for gastric cancer therapeutics.
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Affiliation(s)
- Yijing Shen
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
| | - Xiuchong Yu
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.,Ningbo No. 1 Hospital Affiliated to Ningbo University School of Medicine
| | - Yao Ruan
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
| | - Zhe Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
| | - Yaoyao Xie
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
| | - Zhilong Yan
- Ningbo No. 1 Hospital Affiliated to Ningbo University School of Medicine
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
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Li J, Yang Y, Xu D, Cao L. hsa_circ_0023409 Accelerates Gastric Cancer Cell Growth and Metastasis Through Regulating the IRS4/PI3K/AKT Pathway. Cell Transplant 2021; 30:963689720975390. [PMID: 33439739 PMCID: PMC7809302 DOI: 10.1177/0963689720975390] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/08/2020] [Accepted: 10/23/2020] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is a big threat to human life and health. Circular RNAs (circRNAs), a subclass of noncoding RNAs, were reported to play a critical role in GC progression. Here, we investigated the role of a novel circRNA named hsa_circ_0023409 in GC and its mechanism. Hsa_circ_0023409 expression in GC and adjacent tissues was examined by quantitative real-time polymerase chain reaction and in situ hybridization. The functions of hsa_circ_0023409 in GC cells were assessed both in vitro and in vivo. Immunofluorescence staining was performed for the localization of hsa_circ_0023409 and miR-542-3p in cells. The interaction between hsa_circ_0023409 and miR-542-3p, and miR-542-3p and insulin receptor substrate 4 (IRS4) was detected by dual-luciferase reporter assay. The effect of hsa_circ_0023409, miR-542-3p, and IRS4 on IRS4/phosphatidylinositol 3-kinase (PI3K)/AKT pathway was detected by western blot. The results showed that hsa_circ_0023409 was mainly located in cytoplasm and highly expressed in GC tissues and cells. Moreover, hsa_circ_0023409 showed positive correlation with tumor size, histological grade, and tumor-node-metastasis staging of GC patients. Functional studies showed that hsa_circ_0023409 promoted cell viability, proliferation, migration, and invasion and suppressed apoptosis in GC. Mechanism studies demonstrated that hsa_circ_0023409 upregulated IRS4 via sponging miR-542-3p in GC cells. Furthermore, IRS4 overexpression activated the PI3K/AKT pathway and reversed the inhibitory effect of hsa_circ_0023409 knockdown on the PI3K/AKT pathway. Taken together, we prove that hsa_circ_0023409 activates IRS4/PI3K/AKT pathway by acting as a sponge for miR-542-3p, thus promoting GC progression, indicating that hsa_circ_0023409 may serve as a potential target for treatment of GC and prognosis of GC patients.
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Affiliation(s)
- Jian Li
- Department of Gastrointestinal Surgery, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang city, Jiangxi Province, China
| | - Yongjing Yang
- Department of Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun City, Jilin Province, China
| | - Dequan Xu
- Department of Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun City, Jilin Province, China
| | - Ling Cao
- Department of Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun City, Jilin Province, China
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Li Y, Liu J, Piao J, Ou J, Zhu X. Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA-105/SOX9/Wnt/β-catenin axis. IUBMB Life 2020; 73:159-176. [PMID: 33220169 DOI: 10.1002/iub.2415] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/06/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023]
Abstract
Emerging evidence suggests the important involvements of circular RNAs (circRNAs) in cancer progression. This study focuses on the function of Circ_0109046 on the malignancy of endometrial carcinoma (EC) cells and the molecules involved. First, high expression of Circ_0109046 was found in EC tissues compared to the adjacent tissues, and it predicted unfavorable prognosis in patients. Similarly, high expression of Circ_0109046 was confirmed in EC cells relative to that in normal endometrial epithelial cells. Silencing of Circ_0109046 in AN3-CA cells inhibited proliferation and aggressiveness but increased apoptosis of cells. Circ_0109046 was mainly sub-localized in cytoplasm, and it mediated SOX9 expression through sponging microRNA (miR)-105. The proliferation and aggressiveness of EC cells suppressed by Circ_0109046 downregulation was recovered upon SOX9 overexpression. SOX9 activated the Wnt/β-catenin pathway. Furthermore, downregulation of Circ_0109046 reduced the growth of xenograft tumors in nude mice. This study evidenced that Circ_0109046 upregulates SOX9 expression through sponging miR105, leading to activation of Wnt/β-catenin signaling and the malignant growth of EC. This study may offer novel understanding in EC treatment.
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Affiliation(s)
- Yanyan Li
- Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China
| | - Jinyu Liu
- Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China
| | - Jinxia Piao
- Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China
| | - Jian Ou
- Department of Radiotherapy of Gynecologic Oncology, Jilin Cancer Hospital, Changchun, China
| | - Xiaoyan Zhu
- Department 1 of Gynecological Oncology, Jilin Cancer Hospital, Changchun, China
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Fu LY, Wang SW, Hu MY, Jiang ZL, Shen LL, Zhou YP, Guo JM, Hu YR. Circular RNAs in liver diseases: Mechanisms and therapeutic targets. Life Sci 2020; 264:118707. [PMID: 33144187 DOI: 10.1016/j.lfs.2020.118707] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/22/2020] [Accepted: 10/30/2020] [Indexed: 02/07/2023]
Abstract
Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.
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Affiliation(s)
- Li-Yun Fu
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Science, Ningbo 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China.
| | - Shu-Wei Wang
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China
| | - Meng-Yuan Hu
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China
| | - Zhen-Luo Jiang
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
| | - Li-Li Shen
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
| | - Yu-Ping Zhou
- Department of Gastroenterology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo 315020, China
| | - Jun-Ming Guo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China
| | - Yao-Ren Hu
- Department of Infection and Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Science, Ningbo 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, China
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Yin L, Tang Y, Jiang M. Research on the circular RNA bioinformatics in patients with acute myocardial infarction. J Clin Lab Anal 2020; 35:e23621. [PMID: 33063376 PMCID: PMC7891515 DOI: 10.1002/jcla.23621] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/16/2020] [Accepted: 09/18/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Through the detection of circular RNA (circRNA) using expression profiling chips, we searched for circRNAs related to acute myocardial infarction (AMI) and explored their relationship and possible mechanisms with AMI. METHOD The study subjects included 3 AMI patients and 3 controls, and circRNA expression profiling analysis was performed using a microarray gene chip to identify circRNAs with large differences in expression between groups and to construct a circRNA-miRNA network. RESULTS Compared with the control group, there were 650 differentially expressed circRNAs found in AMI patients (P < .05, fold change > 2), including 535 up-regulated circRNAs, such as hsa_circ_0050908, hsa_circRNA4010-22, hsa_circ_0081241, hsa_circ_0010551, hsa_circRNA4010-20, hsa_circRNA14702, hsa_circ_0115392, has_circRNA1825-44, has_circRNA8493-7, and hsa_circ_0025097. Furthermore, there were 115 down-regulated circRNAs, such as hsa_circ_0066439, hsa_circ_0054211, hsa_circ_0095920, hsa_circ_0122984, hsa_circ_0113067, hsa_circ_0039155, hsa_circRNA4014-45, hsa_circ_0122979, hsa_circ_0059665, and hsa_circ_0009319. The circRNAs hsa_circ_0066439, hsa_circ_0081241, and hsa_circ_0122984 can regulate multiple signal pathways to participate in the AMI process through hsa-miR-1254, hsa-miR-328-5p, and other miRNAs. In addition, the expression of circRNA-miRNA in peripheral blood is related to the network. Differentially expressed circRNAs are involved in chromatin organization, chromatin-modifying enzymes, signal transduction, lysine degradation, the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion, and a variety of other pathways, such as myocardial infarction, coronary heart disease, hypertension, and other diseases. The gene ontology analysis results show that molecular function mainly involves binding and molecular structural activity, whereas the biological process mainly involves a single biological process, a cellular component for organization, and a cellular process, and the cellular component mainly involves a protein complex, an extracellular matrix, and a membrane. CONCLUSION circRNA and microRNA interact to participate in the development of AMI. circRNA may be involved in the pathogenesis of AMI.
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Affiliation(s)
- Lianli Yin
- Department of Clinical Laboratory, Nanning Second People's Hospital, the Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yinghua Tang
- Department of Clinical Laboratory, Guangxi Hospital Of Traditional Chinese Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Minghe Jiang
- Emergency cardiothoracic Department, Nanning Second People's Hospital, the Third Affiliated Hospital of Guangxi Medical University,, Nanning, Guangxi, China
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Lin J, Liao S, Li E, Liu Z, Zheng R, Wu X, Zeng W. circCYFIP2 Acts as a Sponge of miR-1205 and Affects the Expression of Its Target Gene E2F1 to Regulate Gastric Cancer Metastasis. MOLECULAR THERAPY. NUCLEIC ACIDS 2020; 21:121-132. [PMID: 32526476 PMCID: PMC7286931 DOI: 10.1016/j.omtn.2020.05.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/07/2020] [Accepted: 05/08/2020] [Indexed: 02/05/2023]
Abstract
Accumulating evidence suggested that circular RNAs (circRNAs) play critical roles in the initiation and progression of malignant cancers. However, the roles of circRNAs in gastric cancer (GC) remain largely unknown. In the present study, we investigated the expression of circRNAs in 5 GC tissues with metastasis and 5 GC tissues without metastasis by microarray analysis. We focused on hsa_circ_0003506, which was spliced from CYFIP2 gene located at chr5:156786012-156788606 and finally formed a sense-overlapping circular transcript of 366 nt, and thus we named it circCYFIP2. circCYFIP2 was found to be significantly upregulated in GC tissues and cell lines. High expression of circCYFIP2 was associated with metastasis and poor prognosis of GC patients. Function assays revealed that overexpression or knockdown of circCYFIP2 significantly enhanced or reduced GC cell proliferation and invasion abilities. In mechanism, we found that circCYFIP2 might serve as a competing endogenous RNA (ceRNA) of microRNA-1205 (miR-1205) in GC progression. Besides, E2F1 was found to be a target of miR-1205. Collectively, our findings suggested that circCYFIP2 might serve as an oncogenic circRNA to promote GC progression via the miR-1205/E2F1 axis, which provided a potential therapeutic target for the treatment of GC.
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Affiliation(s)
- Jing Lin
- The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
| | - Shasha Liao
- The First Affiliated Hospital of Shantou University Medical College, Longhu People's Hospital Shantou, Shantou 515041, China
| | - E Li
- The First Affiliated Hospital of Shantou University Medical College, Longhu People's Hospital Shantou, Shantou 515041, China
| | - Zewa Liu
- The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Ruihua Zheng
- The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
| | - Xiaohua Wu
- The First Affiliated Hospital of Shantou University Medical College, Longhu People's Hospital Shantou, Shantou 515041, China
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