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Digby B, Finn S, Ó Broin P. Computational approaches and challenges in the analysis of circRNA data. BMC Genomics 2024; 25:527. [PMID: 38807085 PMCID: PMC11134749 DOI: 10.1186/s12864-024-10420-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 05/15/2024] [Indexed: 05/30/2024] Open
Abstract
Circular RNAs (circRNA) are a class of non-coding RNA, forming a single-stranded covalently closed loop structure generated via back-splicing. Advancements in sequencing methods and technologies in conjunction with algorithmic developments of bioinformatics tools have enabled researchers to characterise the origin and function of circRNAs, with practical applications as a biomarker of diseases becoming increasingly relevant. Computational methods developed for circRNA analysis are predicated on detecting the chimeric back-splice junction of circRNAs whilst mitigating false-positive sequencing artefacts. In this review, we discuss in detail the computational strategies developed for circRNA identification, highlighting a selection of tool strengths, weaknesses and assumptions. In addition to circRNA identification tools, we describe methods for characterising the role of circRNAs within the competing endogenous RNA (ceRNA) network, their interactions with RNA-binding proteins, and publicly available databases for rich circRNA annotation.
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Affiliation(s)
- Barry Digby
- School of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland.
| | - Stephen Finn
- Discipline of Histopathology, School of Medicine, Trinity College Dublin and Cancer Molecular Diagnostic Laboratory, Dublin, Ireland
| | - Pilib Ó Broin
- School of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland
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2
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Zhang D, Zhou Y, Jiao C, Kong H, Zhao Z, Li Y. Circ_0050444 represses esophageal squamous cell carcinoma progression through sponging miR-486-3p to upregulate C10orf91. Cell Cycle 2024; 23:693-702. [PMID: 38867541 PMCID: PMC11229726 DOI: 10.1080/15384101.2024.2357909] [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: 08/03/2023] [Accepted: 05/16/2024] [Indexed: 06/14/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of tumor-related deaths in China. Circ_0050444 has been revealed to be downregulated in ESCC tissues, however, its function and molecular mechanism underlying ESCC progression is unknown. Therefore, we attempted to clarify the functional role and molecular mechanism of circ_0050444 underlying ESCC progression. RT-qPCR and RNase R digestion assays were used to evaluate circ_0050444 expression and stability characteristics in ESCC cells. Gain-of-function assays were conducted to clarify circ_0050444 role in ESCC cell malignant behaviors. Bioinformatics and mechanism experiments were performed to assess the relationship between circ_0050444 or C10orf91 and miR-486-3p in ESCC cells. Rescue assays were conducted to evaluate the regulatory function of the circ_0050444-miR-486-3p-C10orf91 axis in ESCC cellular processes. Circ_0050444 expression was found to be downregulated both in ESCC patient tissues and cell lines. Functionally, circ_0050444 overexpression repressed ESCC cell proliferative, migratory, and invasive capabilities in cultured cells. Mechanistically, circ_0050444 was found to be competitively bound with miR-486-3p to upregulate C10orf91 in ESCC cells. Moreover, the impact of circ_0050444 elevation on ESCC cell proliferation, migration, and invasion was countervailed by C10orf91 silencing. Circ_0050444 presents downregulation and functions as a tumor suppressor in ESCC progression. Circ_0050444 suppresses ESCC proliferation, migration, and invasion through sponging miR-486-3p to upregulate C10orf91, providing a potential new direction for seeking therapeutic plans for ESCC.
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Affiliation(s)
- Dongli Zhang
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Yan Zhou
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Chenyang Jiao
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Hongfang Kong
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Zhibin Zhao
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Yujiang Li
- The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
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Trifylli EM, Kriebardis AG, Koustas E, Papadopoulos N, Vasileiadi S, Fortis SP, Tzounakas VL, Anastasiadi AT, Sarantis P, Papageorgiou EG, Tsagarakis A, Aloizos G, Manolakopoulos S, Deutsch M. The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches. Int J Mol Sci 2023; 24:15563. [PMID: 37958547 PMCID: PMC10649642 DOI: 10.3390/ijms242115563] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 10/21/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Cholangiocarcinomas (CCAs) constitute a heterogeneous group of highly malignant epithelial tumors arising from the biliary tree. This cluster of malignant tumors includes three distinct entities, the intrahepatic, perihilar, and distal CCAs, which are characterized by different epidemiological and molecular backgrounds, as well as prognosis and therapeutic approaches. The higher incidence of CCA over the last decades, the late diagnostic time that contributes to a high mortality and poor prognosis, as well as its chemoresistance, intensified the efforts of the scientific community for the development of novel diagnostic tools and therapeutic approaches. Extracellular vesicles (EVs) comprise highly heterogenic, multi-sized, membrane-enclosed nanostructures that are secreted by a large variety of cells via different routes of biogenesis. Their role in intercellular communication via their cargo that potentially contributes to disease development and progression, as well as their prospect as diagnostic biomarkers and therapeutic tools, has become the focus of interest of several current studies for several diseases, including CCA. The aim of this review is to give a rundown of the current knowledge regarding the emerging role of EVs in cholangiocarcinogenesis and their future perspectives as diagnostic and therapeutic tools.
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Affiliation(s)
- Eleni-Myrto Trifylli
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece;
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Anastasios G. Kriebardis
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Evangelos Koustas
- Oncology Department, General Hospital Evangelismos, 10676 Athens, Greece;
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Nikolaos Papadopoulos
- Second Department of Internal Medicine, 401 General Military Hospital, 115 27 Athens, Greece;
| | - Sofia Vasileiadi
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Sotirios P. Fortis
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Vassilis L. Tzounakas
- Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece; (V.L.T.); (A.T.A.)
| | - Alkmini T. Anastasiadi
- Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece; (V.L.T.); (A.T.A.)
| | - Panagiotis Sarantis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Effie G. Papageorgiou
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Ariadne Tsagarakis
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;
| | - Georgios Aloizos
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece;
| | - Spilios Manolakopoulos
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Melanie Deutsch
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
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Liao W, Du J, Li L, Wu X, Chen X, Feng Q, Xu L, Chen X, Liao M, Huang J, Yuan K, Zeng Y. CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma. J Exp Clin Cancer Res 2023; 42:125. [PMID: 37198696 PMCID: PMC10193609 DOI: 10.1186/s13046-023-02699-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/05/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Increasing evidence shows that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a crucial role in the development of cancers, including intrahepatic cholangiocarcinoma (iCCA). Nevertheless, their functions and exact mechanisms in iCCA progression and metastasis are still unclear. Ipatasertib is a highly selective inhibitor of AKT that inhibits tumor growth by blocking the PI3K/AKT pathway. In addition, phosphatase and tensin homolog (PTEN) can also inhibit the activation of the PI3K/AKT pathway, but it is not clear whether the cZNF215-PRDX-PTEN axis plays a role in the antitumor activity of ipatasertib. METHODS We identified a new circRNA (circZNF215, termed cZNF215) through high-throughput circRNA sequencing (circRNA-seq). In addition, RT‒qPCR, immunoblot assay, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and fluorescence in situ hybridization assay (FISH) were used to investigate the interaction of cZNF215 with peroxiredoxin 1 (PRDX1). Coimmunoprecipitation (Co-IP) assays and duolink in situ proximity ligation assays (PLAs) were conducted to analyze the effects of cZNF215 on the interaction between PRDX1 and PTEN. Finally, we tested the potential effects of cZNF215 on the antitumor activity of ipatasertib with in vivo experiments. RESULTS We found that cZNF215 expression was obviously upregulated in iCCA tissues with postoperative metastases and was correlated with iCCA metastasis and poor outcome in patients with iCCA. We further revealed that overexpression of cZNF215 promoted iCCA cell growth and metastasis in vitro and in vivo, while cZNF215 knockdown had the opposite effect. Mechanistic studies suggested that cZNF215 competitively interacted with PRDX1, which blocked the association between PRDX1 and PTEN, subsequently leading to oxidation-induced inactivation of the PTEN/AKT pathway and finally contributing to iCCA progression and metastasis. Additionally, we also revealed that silencing cZNF215 in iCCA cells had the potential to enhance the antitumor effect of ipatasertib. CONCLUSIONS Our study demonstrates that cZNF215 facilitates iCCA progression and metastasis by regulating the PTEN/AKT pathway and may serve as a novel prognostic predictor in patients with iCCA.
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Affiliation(s)
- Wenwei Liao
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Jinpeng Du
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Lian Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Xianquan Wu
- Department of General Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China
| | - Xing Chen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Qingbo Feng
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Lin Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Xiangzheng Chen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Mingheng Liao
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Jiwei Huang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China
| | - Kefei Yuan
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.
| | - Yong Zeng
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.
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Saengboonmee C, Obchoei S, Sawanyawisuth K, Wongkham S. Revision of potential prognostic markers of cholangiocarcinoma for clinical practice. Expert Rev Anticancer Ther 2023; 23:517-530. [PMID: 37052887 DOI: 10.1080/14737140.2023.2203386] [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: 01/15/2023] [Accepted: 04/12/2023] [Indexed: 04/14/2023]
Abstract
INTRODUCTION Cholangiocarcinoma (CCA) is an aggressive cancer arising from any part of the biliary system. Effective treatment of CCA remains limited, resulting in the poor overall prognosis of patients. The effective prognostic biomarkers for CCA remain lacking, and most are at the research level. AREAS COVERED The incidences of CCAs, classification, genetic and molecular characteristics, and distinct clinical outcomes in each subtype are introduced. The prognostic markers currently used in clinical practice are reviewed. Studies of biomarkers in defining the aggressiveness of CCA, identifying patients with a potential tumor recurrence, and predicting the survival time, are reviewed. Emerging biomarkers discovered from advanced high throughput technology over the past 5 years are updated and summarized. Finally, in-depth and critical revision on the prognostic biomarkers for CCA reported from various sources of specimens, e.g. tissues, blood, bile, etc. are discussed. Conclusion: Many prognostic biomarkers for CCA have been proposed and hold promising clinical value. However, these markers are rarely used in the real clinical world due to several factors. Understanding the roles and importance of these prognostic markers may fundamentally impact the therapeutic management of CCA, and hopefully, improve the development of custom and patient-directed therapies for CCA.
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Affiliation(s)
- Charupong Saengboonmee
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sumalee Obchoei
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
| | - Kanlayanee Sawanyawisuth
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sopit Wongkham
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Circular RNAs in cholangiocarcinoma. Cancer Lett 2023; 553:215980. [PMID: 36336149 DOI: 10.1016/j.canlet.2022.215980] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 11/06/2022]
Abstract
Cholangiocarcinoma (CCA) is the most common primary biliary malignancy with an adverse prognosis. Although its incidence is relatively low, early diagnosis is difficult due to the lack of specific symptoms. Current treatment options for CCA are limited, resulting in a low curative rate. Circular RNAs (circRNAs) have become a new research hotspot in recent years, and they are frequently dysregulated in CCA and may become therapeutic targets and prognostic biomarkers of CCA. Accumulating evidence has demonstrated that numerous dysregulated circRNAs are vital players in the etiopathogenesis of CCA. Aberrant expression of specific circRNAs was correlated with unfavourable clinical characteristics in CCA. Many studies have found that circRNAs are involved in the progression and development of CCA through various mechanisms, including competitive inhibition of miRNAs via the competing endogenous RNA (ceRNA) network, interaction with RNA-binding proteins (RBPs), activation of cancer-related signalling pathways, and regulation of proteins and peptides. Additionally, some circRNAs are involved in the inflammatory microenvironment of CCA and play a crucial role in chemotherapy drug resistance. Thus, they are essential for the early diagnosis and prediction of CCA, and more attention should be given to the roles and mechanisms of circRNAs in CCA. In this review, we summarize the abnormal expression of circRNAs in CCA and the specific inflammatory microenvironment involved, as well as the roles and mechanisms of circRNAs in the occurrence and development of CCA. We also review the latest knowle dge on circRNAs in CCA and discuss the challenges associated with the introduction of circRNAs into clinical practice and their potential clinical value.
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Xiao Y, Qiu M, Tan C, Huang W, Hu S, Jiang X, Guo M, Wang C, Liang J, Wu Y, Li M, Li Q, Qin C. Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer. Front Genet 2022; 13:938672. [PMID: 36313458 PMCID: PMC9597305 DOI: 10.3389/fgene.2022.938672] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 09/23/2022] [Indexed: 08/13/2023] Open
Abstract
As the third most common cancer and the second leading cause of cancer death worldwide, colorectal cancer (CRC) poses a serious threat to people's health. In recent years, circRNA has been widely reported as a new biomarker in CRC, but a comprehensive summary and analysis is lacking. This study aims to evaluate the diagnostic, therapeutic and prognostic significance of circRNAs in CRC by systematically analysing their expression patterns, biological functions and clinical significance in CRC. The literature on circRNA in CRC was searched in the PubMed database and included for analysis after screening according to strict inclusion and exclusion criteria. The UALCAN online tool was used to obtain host gene expression data. The miRTargetLink 2.0 was used to predict target genes for miRNAs action in CRC patients. Cytoscape was used to construct circRNA-miRNA-mRNA interaction networks. From the 236 included papers, we identified 217 circRNAs and their associated 108 host genes and 145 miRNAs. Among the 145 miRNAs, 27 miRNAs had no corresponding target genes. After prediction of target genes and differential analysis, a total of 25 target genes were obtained and a circRNA-miRNA-mRNA interaction network was constructed. Among the 217 circRNAs, 74 were associated with diagnosis, 160 with treatment and 51 with prognosis. And 154 of them function as oncogenes while 58 as tumour suppressor genes. In addition, these circRNAs include 32 exosomal circRNAs, which have unique advantages as biomarkers. In total, we summarize and analyze the expression patterns, biological functions and clinical significance of circRNAs in CRC. In addition, we constructed some new circRNA-miRNA-mRNA regulatory axes based on the miRNAs sponged by circRNAs.
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Affiliation(s)
- Yafei Xiao
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Mengyuan Qiu
- Department of Neurology, Peking University People’s Hospital, Peking University School of Medicine, Beijing, China
| | - Cong Tan
- Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Wanting Huang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shaowen Hu
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Xiaowei Jiang
- Department of Pediatric Orthopaedics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mingjie Guo
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Congcong Wang
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Jingyu Liang
- Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Yimei Wu
- Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Mengmeng Li
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Quanying Li
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Changjiang Qin
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China
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Shen J, Liang C, Su X, Wang Q, Ke Y, Fang J, Zhang D, Duan S. Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis. Biomark Res 2022; 10:72. [PMID: 36175921 PMCID: PMC9524011 DOI: 10.1186/s40364-022-00419-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 09/13/2022] [Indexed: 11/25/2022] Open
Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNAs ranging from 17 to 25 nt in length. miR-637 is down-regulated in most cancers and up-regulated only in clear cell renal cell carcinoma (ccRCC). miR-637 can target 21 protein-coding genes, which are involved in the regulation of cell growth, cell cycle, cell proliferation, epithelial-mesenchymal transition (EMT), cancer cell invasion and metastasis, etc. In glioma, the transcription factor ZEB2 can bind to the miR-637 promoter region and inhibit miR-637 expression. Besides, miR-637 could be negatively regulated by competing endogenous RNA (ceRNAs) comprising 13 circular RNA (circRNAs) and 9 long non-coding RNA (lncRNAs). miR-637 is involved in regulating five signaling pathways, including the Jak/STAT3, Wnt/β-catenin, PI3K/AKT, and ERK signaling pathways. Low miR-637 expression was significantly associated with larger tumors and later tumor node metastasis (TNM) staging in cancer patients. Low miR-637 expression was also associated with poorer overall survival (OS) in cancer patients such as glioblastoma and low-grade gliomas (GBM/LGG), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer (OV). Low expression of miR-637 increases the resistance of colorectal cancer (CRC) and human cholangiocarcinoma (CHOL) cancer cells to three anticancer chemotherapeutics (gemcitabine (dFdC), cisplatin (DDP), and oxaliplatin (OXA)). Our work summarizes the abnormal expression of miR-637 in various cancers, expounds on the ceRNA regulatory network and signaling pathway involved in miR-637, and summarizes the effect of its abnormal expression on the biological behavior of tumor cells. At the same time, the relationship between the expression levels of miR-637 and its related molecules and the prognosis and pathological characteristics of patients was further summarized. Finally, our work points out the insufficiency of miR-637 in current studies and is expected to provide potential clues for future miR-637-related studies.
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Affiliation(s)
- Jinze Shen
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Chenhao Liang
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Xinming Su
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Qurui Wang
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Yufei Ke
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Jie Fang
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China
| | - Dayong Zhang
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China.
| | - Shiwei Duan
- Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, Zhejiang, China.
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Macias RIR, Cardinale V, Kendall TJ, Avila MA, Guido M, Coulouarn C, Braconi C, Frampton AE, Bridgewater J, Overi D, Pereira SP, Rengo M, Kather JN, Lamarca A, Pedica F, Forner A, Valle JW, Gaudio E, Alvaro D, Banales JM, Carpino G. Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions. Gut 2022; 71:1669-1683. [PMID: 35580963 DOI: 10.1136/gutjnl-2022-327099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers.
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Affiliation(s)
- Rocio I R Macias
- Experimental Hepatology and Drug Targeting (HEVEPHARM) group, University of Salamanca, IBSAL, Salamanca, Spain
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Timothy J Kendall
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Matias A Avila
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain
| | - Maria Guido
- Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Cedric Coulouarn
- UMR_S 1242, COSS, Centre de Lutte contre le Cancer Eugène Marquis, INSERM University of Rennes 1, Rennes, France
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Adam E Frampton
- Department of Clinical and Experimental Medicine, University of Surrey, Guildford, Surrey, UK
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Stephen P Pereira
- Institute for Liver & Digestive Health, University College London, London, UK
| | - Marco Rengo
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Jakob N Kather
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Angela Lamarca
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Federica Pedica
- Department of Pathology, San Raffaele Scientific Institute, Milan, Italy
| | - Alejandro Forner
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- BCLC group, Liver Unit, Hospital Clínic Barcelona. IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan W Valle
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jesus M Banales
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome, Italy
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10
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Gao SL, Fan Y, Liu XD, Liu W, Zhao M. circ_0089153 exacerbates breast cancer cells proliferation and metastasis via sponging miR-2467-3p/E2F6. ENVIRONMENTAL TOXICOLOGY 2022; 37:1458-1471. [PMID: 35225430 DOI: 10.1002/tox.23498] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 01/12/2022] [Accepted: 02/13/2022] [Indexed: 06/14/2023]
Abstract
The role of circ_0089153 in breast cancer (BCa) malignancy development was explored. circ_0089153 expression in BCa was analyzed by Gene Expression Omnibus database. Clinical tissues were obtained from 90 BCa patients. Cell counting kit-8 assay, 5-ethnyl-2 deoxyuridine assay and colony formation experiment were applied for proliferation detection. Wound healing assay and Transwell experiment were used for migration and invasion detection. Dual luciferase reporter gene assay, RNA immunoprecipitation assay and RNA pull-down assay were conducted. In vivo growth and metastasis of BCa cells were performed. Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were applied for RNAs and proteins expression. The up-modulated circ_0089153 indicated an unfavorable survival of BCa patients. circ_0089153 knockdown attenuated BCa cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < .01). circ_0089153 was miR-2467-3p sponge. Low miR-2467-3p expression indicated a worse survival of BCa patients. miR-2467-3p overexpression reduced BCa cells proliferation, migration, invasion and EMT (P < .05). circ_0089153 enhanced BCa cells proliferation, migration, invasion and EMT by sponging miR-2467-3p (P < .05). E2F6 was directly suppressed by miR-2467-3p. E2F6 high expression in BCa patients associated with worse survival. circ_0089153 knockdown suppressed in vivo BCa cells growth and lung metastasis (P < .01). circ_0089153 was an oncogene in breast cancer, which enhanced proliferation and metastasis through sponging miR-2467-3p/E2F6. circ_0089153 was suggested to be a potential target for BCa target treatment.
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Affiliation(s)
- Shu-Lan Gao
- Department of Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Ying Fan
- Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiao-Dan Liu
- Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Wei Liu
- Department of Geriatrics, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Man Zhao
- Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
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11
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The emerging landscape of exosomal CircRNAs in solid cancers and hematological malignancies. Biomark Res 2022; 10:28. [PMID: 35505392 PMCID: PMC9066734 DOI: 10.1186/s40364-022-00375-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/05/2022] [Indexed: 12/24/2022] Open
Abstract
Circular RNAs (circRNAs) are a type of recently discovered noncoding RNA. They exert their biological functions by competitively binding to microRNAs (miRNAs) as miRNA sponges, promoting gene transcription and participating in the regulation of selective splicing, interacting with proteins and being translated into proteins. Exosomes are derived from intracavitary vesicles (ILVs), which are formed by the inward budding of multivesicular bodies (MVBs), and exosome release plays a pivotal role in intercellular communication. Accumulating evidence indicates that circRNAs in exosomes are associated with solid tumor invasion and metastasis. Additionally, emerging studies in the last 1 ~ 2 years have revealed that exosomal circRNA also have effect on hematological malignancies. In this review, we outline the properties and biological functions of circRNAs and exosomes. In particular, we summarize in detail the mechanism and roles of exosomal circRNAs and highlight their application as novel biomarkers in malignant tumors.
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12
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Ye D, Gong M, Deng Y, Fang S, Cao Y, Xiang Y, Shen Z. Roles and clinical application of exosomal circRNAs in the diagnosis and treatment of malignant tumors. J Transl Med 2022; 20:161. [PMID: 35382838 PMCID: PMC8981684 DOI: 10.1186/s12967-022-03367-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 03/26/2022] [Indexed: 02/07/2023] Open
Abstract
Exosomes are microvesicles secreted by cells. They contain a variety of bioactive substances with important roles in intercellular communication. Circular RNA (circRNA), a type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5′ caps or 3′ poly(A) tails. It is structurally stable, widely distributed, and tissue specific. CircRNAs mainly act as microRNA sponges and have important regulatory roles in gene expression; they are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumor patients can modulate tumor proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumors, and also represent ideal targets for early precision therapeutic intervention. This review provides a theoretical basis for exploring the applications of exosomal circRNAs in malignant tumor diagnosis and treatment. We describe the biological functions of exosomal circRNAs in the occurrence and development of malignant tumors, their potential utility in diagnosis and treatment, and possible mechanisms.
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Affiliation(s)
- Dong Ye
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
| | - Mengdan Gong
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Yongqin Deng
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Shuai Fang
- Department of Thoracic Surgery, Affiliated Hospital of Ningbo University, Ningbo, 315020, Zhejiang, China
| | - Yujie Cao
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Yizhen Xiang
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Zhisen Shen
- Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
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13
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Upregulation of circ_0059961 suppresses cholangiocarcinoma development by modulating miR-629-5p/SFRP2 axis. Pathol Res Pract 2022; 234:153901. [DOI: 10.1016/j.prp.2022.153901] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/03/2022] [Accepted: 04/15/2022] [Indexed: 12/25/2022]
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14
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Li T, Liu W, Wang C, Wang M, Hui W, Lu J, Gao F. Multidimension Analysis of the Prognostic Value, Immune Regulatory Function, and ceRNA Network of LY6E in Individuals with Colorectal Cancer. J Immunol Res 2022; 2022:5164265. [PMID: 35310607 PMCID: PMC8933097 DOI: 10.1155/2022/5164265] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/09/2022] [Accepted: 02/23/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Lymphocyte antigen 6 complex, locus E (LY6E) is abnormally expressed in several cancers and is associated with poor outcomes. However, the biological role of LY6E in colorectal cancer (CRC) remains largely unknown. Hence, we aimed to evaluate the expression levels, prognostic value, biological functions, and immune effects of LY6E via pan-cancer and CRC analyses using multiple databases. METHODS We analyzed the expression pattern of LY6E in various cancers. The prognostic value of LY6E expression was identified using the Kaplan-Meier analysis and the Cox regression models. We used gene set enrichment analysis (GSEA) to identify the potential functions of LY6E. Correlations between the LY6E expression and various factors, including LY6E methylation level, copy number variation (CNV), microsatellite instability (MSI), and immune checkpoint genes, were also analyzed. The levels of LY6E expression and immune infiltration were analyzed using CIBERSORT. We constructed a regulatory network that was in compliance with the competing endogenous RNA (ceRNA) hypothesis. A ceRNA expression-based nomogram was established. Real-time PCR (qRT-PCR) was applied to validate the expression of LY6E-related ceRNA in CRC cell lines. RESULTS LY6E is overexpressed in several tumor types, including CRC, and patients with high expression levels of LY6E have a poor prognosis. The Kaplan-Meier analysis and Cox regression analysis showed that LY6E could be considered a favorable prognostic factor in TCGA and GEO cohort. The results of GSEA showed that high LY6E expression levels were associated with immune-related pathways, such as those involved in antigen processing and presentation and the intestinal immune network for IgA production. Six methylation sites of LY6E that were associated with prognostic survival were screened. Moreover, the high levels of LY6E expression were correlated with copy number gain, microsatellite instability high, and immunotherapy response. The results of CIBERSORT analysis demonstrated that the LY6E expression levels were correlated with the infiltration of multiple immune cells, especially T cells. Then, we constructed a ceRNA network (LINC00963/miR-92a-3p/LY6E) and validated it using qRT-PCR. A predictive ceRNA-based nomogram was established and validated. CONCLUSION The oncogenic LY6E may serve as a promising marker for the diagnosis and treatment of CRC.
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Affiliation(s)
- Ting Li
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Weidong Liu
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Chun Wang
- Department of Pathology, People's Hospital of Xinjiang Uygur Autonomous Region, China
| | - Man Wang
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Wenjia Hui
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Jiajie Lu
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
| | - Feng Gao
- Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, China
- Xinjiang Clinical Research Center for Digestive Diseases, China
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15
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Li G, Wang D, Zhang Y, Liang C, Xiao Q, Luo J. Using Graph Attention Network and Graph Convolutional Network to Explore Human CircRNA-Disease Associations Based on Multi-Source Data. Front Genet 2022; 13:829937. [PMID: 35198012 PMCID: PMC8859418 DOI: 10.3389/fgene.2022.829937] [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: 12/06/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
Cumulative research studies have verified that multiple circRNAs are closely associated with the pathogenic mechanism and cellular level. Exploring human circRNA-disease relationships is significant to decipher pathogenic mechanisms and provide treatment plans. At present, several computational models are designed to infer potential relationships between diseases and circRNAs. However, the majority of existing approaches could not effectively utilize the multisource data and achieve poor performance in sparse networks. In this study, we develop an advanced method, GATGCN, using graph attention network (GAT) and graph convolutional network (GCN) to detect potential circRNA-disease relationships. First, several sources of biomedical information are fused via the centered kernel alignment model (CKA), which calculates the corresponding weight of different kernels. Second, we adopt the graph attention network to learn latent representation of diseases and circRNAs. Third, the graph convolutional network is deployed to effectively extract features of associations by aggregating feature vectors of neighbors. Meanwhile, GATGCN achieves the prominent AUC of 0.951 under leave-one-out cross-validation and AUC of 0.932 under 5-fold cross-validation. Furthermore, case studies on lung cancer, diabetes retinopathy, and prostate cancer verify the reliability of GATGCN for detecting latent circRNA-disease pairs.
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Affiliation(s)
- Guanghui Li
- School of Information Engineering, East China Jiaotong University, Nanchang, China
| | - Diancheng Wang
- School of Information Engineering, East China Jiaotong University, Nanchang, China
| | - Yuejin Zhang
- School of Information Engineering, East China Jiaotong University, Nanchang, China
| | - Cheng Liang
- School of Information Science and Engineering, Shandong Normal University, Jinan, China
| | - Qiu Xiao
- College of Information Science and Engineering, Hunan Normal University, Changsha, China
| | - Jiawei Luo
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
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16
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Louis C, Leclerc D, Coulouarn C. Emerging roles of circular RNAs in liver cancer. JHEP Rep 2022; 4:100413. [PMID: 35036887 PMCID: PMC8749337 DOI: 10.1016/j.jhepr.2021.100413] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 11/16/2021] [Accepted: 11/18/2021] [Indexed: 12/22/2022] Open
Abstract
Hepatocellular carcinoma and cholangiocarcinoma are the most common primary liver tumours, whose incidence and associated mortality have increased over recent decades. Liver cancer is often diagnosed late when curative treatments are no longer an option. Characterising new molecular determinants of liver carcinogenesis is crucial for the development of innovative treatments and clinically relevant biomarkers. Recently, circular RNAs (circRNAs) emerged as promising regulatory molecules involved in cancer onset and progression. Mechanistically, circRNAs are mainly known for their ability to sponge and regulate the activity of microRNAs and RNA-binding proteins, although other functions are emerging (e.g. transcriptional and post-transcriptional regulation, protein scaffolding). In liver cancer, circRNAs have been shown to regulate tumour cell proliferation, migration, invasion and cell death resistance. Their roles in regulating angiogenesis, genome instability, immune surveillance and metabolic switching are emerging. Importantly, circRNAs are detected in body fluids. Due to their circular structure, circRNAs are often more stable than mRNAs or miRNAs and could therefore serve as promising biomarkers - quantifiable with high specificity and sensitivity through minimally invasive methods. This review focuses on the role and the clinical relevance of circRNAs in liver cancer, including the development of innovative biomarkers and therapeutic strategies.
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Key Words
- ASO, antisense oligonucleotide
- CCA, cholangiocarcinoma
- CLIP, cross-linking immunoprecipitation
- EMT, epithelial-to-mesenchymal transition
- EVs, extracellular vesicles
- HCC, hepatocellular carcinoma
- HN1, haematopoietic- and neurologic-expressed sequence 1
- IRES, internal ribosome entry sites
- NGS, next-generation sequencing
- QKI, Quaking
- RBP, RNA-binding protein
- RISC, RNA-induced silencing complex
- TAM, tumour-associated macrophage
- TSB, target site blockers
- biomarker
- cancer hallmarks
- cholangiocarcinoma
- circRNA
- circRNA, circular RNA
- hepatocellular carcinoma
- miRNA, microRNA
- shRNA, small-hairpin RNA
- snRNP, small nuclear ribonuclear proteins
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Affiliation(s)
- Corentin Louis
- Inserm, Univ Rennes 1, COSS (Chemistry, Oncogenesis Stress Signaling), UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France
| | - Delphine Leclerc
- Inserm, Univ Rennes 1, COSS (Chemistry, Oncogenesis Stress Signaling), UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France
| | - Cédric Coulouarn
- Inserm, Univ Rennes 1, COSS (Chemistry, Oncogenesis Stress Signaling), UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France
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17
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[Research Progress in CircRNA and Radiotherapy Resistance of Non-small Cell Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2021; 24:770-776. [PMID: 34802208 PMCID: PMC8607291 DOI: 10.3779/j.issn.1009-3419.2021.101.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
As the main type of lung cancer, non-small cell lung cancer (NSCLC) is a common cancer which is characterized by low 5-year survival rate and worse prognosis. Nowadays, some studies show that the low survival rate and worse prognosis are due to the resistance to radiotherapy caused by circRNA. Therefore, to find out the relationship between circRNA and radiotherapy resistance of NSCLC was imoprtant. According to research the relevant literatures, the relationship between circRNA and radiotherapy resistance of NSCLC was explored. CircRNA plays an important role in the invasion, metastasis, proliferation and treatment resistance of NSCLC. The radiation resistance of tumor cells induced by circRNA has become a crucial problem in radiotherapy. CircRNA plays an important role in the radiotherapy resistance of NSCLC.
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18
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Jiang W, Pan S, Chen X, Wang ZW, Zhu X. The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy. Mol Cancer 2021; 20:116. [PMID: 34496886 PMCID: PMC8424797 DOI: 10.1186/s12943-021-01406-7] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/08/2021] [Indexed: 12/15/2022] Open
Abstract
Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.
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Affiliation(s)
- Wenxiao Jiang
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027 Zhejiang China
| | - Shuya Pan
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027 Zhejiang China
| | - Xin Chen
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027 Zhejiang China
| | - Zhi-wei Wang
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027 Zhejiang China
| | - Xueqiong Zhu
- Departmant of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027 Zhejiang China
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19
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Abstract
Objective Circular RNA (circRNA) plays a vital role in the development and progression of malignancies, however, the function of circRNAs in cholangiocarcinoma (CCA) remains unexplored. The aim of this study was to investigate circRNA expression in CCA versus para-cancer tissues, and elucidate any potential associated mechanisms. Methods Differential expression of circRNAs between CCA and para-cancer tissue was analysed by microarray hybridization, and validated by real-time quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The downstream pathway was investigated using bioinformatics and qRT–PCR. Results Microarray hybridization revealed 10 circRNAs with > 3-fold increased expression versus para-cancer (circRNA_002172, circRNA_002144, circRNA_001588, circRNA_000166, circRNA_000585, circRNA_000167, circRNA_402608, circRNA_006853, circRNA_001589, circRNA_008882), and three circRNAs with > 3-fold decreased expression (circRNA_406083, circRNA_104940, circRNA_006349). CircRNA_000585 was shown by qRT-PCR to be upregulated in tumour versus paired para-cancer tissue from 15 patients with CCA. Bioinformatics analysis revealed a potential pathway comprising circRNA_000585/microRNA-615-5p/angiomotin (AMOT)/Yes associated protein 1 (YAP) in CCA. RT–PCR validation of crucial molecule expression showed downregulation of miR-615-5p, and upregulation of AMOT and YAP in CCA tumours. Conclusion Multiple circRNAs are dysregulated in CCA. CircRNA_000585 is upregulated in CCA, and may function by a circRNA_000585/miR-615-5p/AMOT/YAP pathway, which may be a novel CCA pathway.
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Affiliation(s)
- Fengming Yi
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, P.R. China.,JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, P.R. China
| | - Longxiang Xin
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, P.R. China.,Jiangxi Cancer hospital, Nanchang, P.R. China
| | - Long Feng
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, P.R. China.,JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, P.R. China
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20
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Wang H, Zeng X, Zheng Y, Wang Y, Zhou Y. Exosomal circRNA in Digestive System Tumors: The Main Player or Coadjuvants? Front Oncol 2021; 11:614462. [PMID: 34249673 PMCID: PMC8264426 DOI: 10.3389/fonc.2021.614462] [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: 10/06/2020] [Accepted: 06/10/2021] [Indexed: 12/20/2022] Open
Abstract
Exosomes are a type of extracellular microvesicles with a diameter of 40–160 nm. Circular RNA (circRNA) is a type of closed circular RNA molecule that is highly conserved in evolution. Exosomal circRNA plays a vital role in the proliferation, invasion, migration, and drug resistance of digestive system tumors. In this study, we used The Cancer Genome Atlas (TCGA) database, UALCAN, Python crawler, miRTargetLink Human, Database for Annotation, Visualization, and Integrated Discovery (DAVID), micBioinformatic online tool, and Cytoscape software (3.7.1). The results showed that circ-RanGAP1 in gastric cancer, circUHRF1 in hepatocellular carcinoma, and circFMN2 in colorectal cancer regulate the malignant behavior of tumors and affect the expression of their host gene through sponging miR-877-3p, miR-449c-5p, and miR-1182, respectively. Twenty exosomal circRNAs regulate 6,570 target genes through sponging 23 miRNAs. Firstly, 270 of those target genes are regulated by two or more miRNAs, which are highly correlated with 83 tumor-related pathways and six Kyoto Encyclopedia of Genes and Genomes pathways. Secondly, 1,146 target genes were significantly differentially expressed in corresponding digestive system tumors, and functional enrichment analysis revealed that 78 of those were involved in 20 cancer-related pathways. In short, the bioinformatics analysis showed that these exosomal circRNAs are stably expressed in body fluids, and regulate the occurrence and development of gastric cancer, hepatocellular carcinoma, colorectal cancer, and other digestive system tumors through sponging miRNAs. Exosomal circRNAs may be used as biomarkers for the diagnosis of disease and identification of effective therapeutic targets in the future, as well as improve the prognosis of patients with digestive system tumors.
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Affiliation(s)
- Haoying Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Xi Zeng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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21
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Luo R, Liu M, Yang Q, Cheng H, Yang H, Li M, Bai X, Wang Y, Zhang H, Wang S, Xie T, Tian Q. Emerging Diagnostic Potential of Tumor-derived Exosomes. J Cancer 2021; 12:5035-5045. [PMID: 34234872 PMCID: PMC8247367 DOI: 10.7150/jca.59391] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/23/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes carry genetic information originating from their parental cells, raising their possibility as novel noninvasive biomarkers for cancer. Tumor-derived exosomes (TEXs) have a variety of endogenous cargos that reflect the pathophysiology status and information of tumor cells. TEXs are increasingly being recognized as potential biomarkers for cancer diagnosis prognosis, and monitoring. It is important to develop a variety of sensitive methods, including probes and biomaterials to isolate exosomes. A variety of approaches for detecting exosomes have been established. By combining exosome DNA and RNA sequencing tools, exosome proteomics analysis and immunoassay technology, it is expected that exosomes will gain widespread use in the diagnosis and treatment of cancer.
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Affiliation(s)
- Ruhua Luo
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Mengmeng Liu
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Qian Yang
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Huijuan Cheng
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Huimin Yang
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Minhui Li
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xue Bai
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Yue Wang
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Honghua Zhang
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Shuling Wang
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Tian Xie
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Qingchang Tian
- College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
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22
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Liu S, Li Q, Ma Y, Corpe C, Wang J. Circular RNAs as novel potential biomarkers for pancreatic cancer. J Cancer 2021; 12:4604-4615. [PMID: 34149924 PMCID: PMC8210554 DOI: 10.7150/jca.58640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/19/2021] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related deaths in the United States, and the vast majority of these malignancies are pancreatic ductal adenocarcinomas (PDAC), but there is still a lack of early detection biomarkers for PaCa. Unlike linear RNAs, circRNAs form covalently closed continuous loops and can act as mammalian gene regulators. They may be diagnostic or predictive biomarkers for some tumors, also be novel potential therapeutic targets in different diseases. This review focuses on (1) the biogenesis of circRNAs, RNA binding proteins (RBPs) and complementary sequences of circRNAs; (2) the characteristics of circRNAs which allow them to interact with miRNAs; (3) the roles of circRNAs playing in the regulation of gene expression, cell behavior and cancer, and their potential role as novel biomarkers and therapeutic targets in pancreatic cancer.
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Affiliation(s)
- Shanshan Liu
- Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai 201508, China
| | - Qiuyue Li
- Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai 201508, China
| | - Yan Ma
- Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai 201508, China
| | - Christopher Corpe
- King's College London, London, Nutritional Science Department, 150 Stamford street, waterloo, London, SE19NH, United Kingdom
| | - Jin Wang
- Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai 201508, China
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23
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Lyu L, Yang W, Yao J, Wang H, Zhu J, Jin A, Liu T, Wang B, Zhou J, Fan J, Yang X, Guo W. The diagnostic value of plasma exosomal hsa_circ_0070396 for hepatocellular carcinoma. Biomark Med 2021; 15:359-371. [PMID: 33666515 DOI: 10.2217/bmm-2020-0476] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 01/21/2021] [Indexed: 12/24/2022] Open
Abstract
Aim: We aimed to identify novel exosomal circular RNAs for hepatocellular carcinoma (HCC) diagnosis. Materials & methods: Exosomes were extracted and characterized. The expression level of exosomal circRNAs were verified via quantitative real-time PCR. The diagnostic value of candidate circRNAs was evaluated according to the receiver operating characteristic curve analysis. Results: The exosomal circ_0070396 significantly elevated in HCC patients than other control groups and it performed better in distinguishing HCC patients from healthy donors than that of α-fetoprotein. Combination of two above markers exerted greater diagnostic performance. Exosomal circ_0070396 could discriminate HCC individuals from patients with chronic hepatitis B and liver cirrhosis. Intriguingly, exosomal circ_0070396 was positively correlated with HCC progression. Conclusion: Exosomal circ_0070396 may be a potential biomarker for HCC detection and management.
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Affiliation(s)
- Lihua Lyu
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenjing Yang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiayi Yao
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Wang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Zhu
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Anli Jin
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Te Liu
- Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Beili Wang
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis & Cancer Invasion, Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis & Cancer Invasion, Ministry of Education, Shanghai, China
| | - Xinrong Yang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis & Cancer Invasion, Ministry of Education, Shanghai, China
| | - Wei Guo
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
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24
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Gao Y, Qin Y, Wan C, Sun Y, Meng J, Huang J, Hu Y, Jin H, Yang K. Small Extracellular Vesicles: A Novel Avenue for Cancer Management. Front Oncol 2021; 11:638357. [PMID: 33791224 PMCID: PMC8005721 DOI: 10.3389/fonc.2021.638357] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 02/01/2021] [Indexed: 12/18/2022] Open
Abstract
Extracellular vesicles are small membrane particles derived from various cell types. EVs are broadly classified as ectosomes or small extracellular vesicles, depending on their biogenesis and cargoes. Numerous studies have shown that EVs regulate multiple physiological and pathophysiological processes. The roles of small extracellular vesicles in cancer growth and metastasis remain to be fully elucidated. As endogenous products, small extracellular vesicles are an ideal drug delivery platform for anticancer agents. However, several aspects of small extracellular vesicle biology remain unclear, hindering the clinical implementation of small extracellular vesicles as biomarkers or anticancer agents. In this review, we summarize the utility of cancer-related small extracellular vesicles as biomarkers to detect early-stage cancers and predict treatment outcomes. We also review findings from preclinical and clinical studies of small extracellular vesicle-based cancer therapies and summarize interventional clinical trials registered in the United States Food and Drug Administration and the Chinese Clinical Trials Registry. Finally, we discuss the main challenges limiting the clinical implementation of small extracellular vesicles and recommend possible approaches to address these challenges.
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Affiliation(s)
| | | | | | | | | | | | | | - Honglin Jin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kunyu Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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25
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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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26
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Merdrignac A, Papoutsoglou P, Coulouarn C. Long Noncoding RNAs in Cholangiocarcinoma. Hepatology 2021; 73:1213-1226. [PMID: 32865244 DOI: 10.1002/hep.31534] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/30/2020] [Accepted: 08/13/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Aude Merdrignac
- InsermUniv RennesNuMeCan (Nutrition Metabolisms and Cancer)UMR_S 1241CHU Rennes, F-35000RennesFrance
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27
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Naseer M, Hadi S, Syed A, Safdari A, Tahan V. Exosomes: A new frontier under the spotlight for diagnosis and treatment of gastrointestinal diseases. World J Meta-Anal 2021; 9:12-28. [DOI: 10.13105/wjma.v9.i1.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/15/2020] [Accepted: 02/22/2021] [Indexed: 02/06/2023] Open
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28
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Masi LN, Lotufo PA, Ferreira FM, Rodrigues AC, Serdan TDA, Souza‐Siqueira T, Braga AA, Saldarriaga MEG, Alba‐Loureiro TC, Borges FT, Cury DP, Hirata MH, Gorjão R, Pithon‐Curi TC, Lottenberg SA, Fedeli LMG, Nakaya HTI, Bensenor IJM, Curi R, Hirabara SM. Profiling plasma-extracellular vesicle proteins and microRNAs in diabetes onset in middle-aged male participants in the ELSA-Brasil study. Physiol Rep 2021; 9:e14731. [PMID: 33587339 PMCID: PMC7883809 DOI: 10.14814/phy2.14731] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/29/2020] [Accepted: 01/04/2021] [Indexed: 12/15/2022] Open
Abstract
We measured plasma-derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle-aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil). Mass spectrometry revealed decreased IGHG-1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR-141-3p and downregulation of miR-324-5p and -376c-3p compared with the NG and GI groups. The DM and GI groups showed increased miR-26b-5p expression compared with that in the NG group. The DM group showed decreased miR-374b-5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
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Affiliation(s)
- Laureane N. Masi
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Paulo A. Lotufo
- Center for Clinical and Epidemiologic ResearchUniversity of Sao PauloSao PauloBrazil
| | | | - Alice C. Rodrigues
- Department of PharmacologyInstitute of Biomedical SciencesUniversity of Sao PauloSao PauloBrazil
| | - Tamires D. A. Serdan
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Talita Souza‐Siqueira
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Aécio A. Braga
- Faculty of Pharmaceutical SciencesUniversity of São PauloSao PauloBrazil
| | | | - Tatiana C. Alba‐Loureiro
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Fernanda T. Borges
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Diego P. Cury
- Department of AnatomyInstitute of Biomedical SciencesUniversity of Sao PauloSao PauloBrazil
| | - Mario H. Hirata
- Faculty of Pharmaceutical SciencesUniversity of São PauloSao PauloBrazil
| | - Renata Gorjão
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Tania C. Pithon‐Curi
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
| | - Simão A. Lottenberg
- Faculty of MedicineUniversity of Sao PauloHospital das ClínicasSao PauloBrazil
| | - Ligia M. G. Fedeli
- Center for Clinical and Epidemiologic ResearchUniversity of Sao PauloSao PauloBrazil
| | - Helder T. I. Nakaya
- Department of PharmacologyInstitute of Biomedical SciencesUniversity of Sao PauloSao PauloBrazil
| | | | - Rui Curi
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
- Butantan InstituteSão PauloBrazil
| | - Sandro M. Hirabara
- Interdisciplinary Post‐graduate Program in Health SciencesCruzeiro do Sul UniversitySao PauloBrazil
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29
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Liu J, Qiao X, Liu J, Zhong M. Identification of circ_0089153/miR-608/EGFR p53 axis in ameloblastoma via MAPK signaling pathway. Oral Dis 2021; 28:756-770. [PMID: 33523578 DOI: 10.1111/odi.13788] [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: 09/22/2020] [Revised: 01/19/2021] [Accepted: 01/24/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This study investigated the role of circular RNAs (circRNAs) in the pathogenesis of ameloblastoma (AB), identifying potential novel targets for future targeted therapy. MATERIALS AND METHODS CircRNA and microRNA (miRNA) profiling in AB were built with microarrays. Six novel circRNAs were validated, circ-miRNA networks were delineated. Hsa-miR-608 was filtered over cross-comparison between database screening, miRNA microarray and validated. Circ-miRNA binding sponge was validated via luciferase reporter assay. Downstream mRNAs were screened. Regulation between miRNAs and mRNAs was confirmed in vitro. Gene interaction networks and circRNA-miRNA-mRNA interaction pathway enrichment analyses were established. RESULTS Six differentially expressed circRNAs were selected and validated. According to miRNAs and pathways predicted, six correlated miRNAs were selected, hsa-miR-608 was filtered and validated. The hsa_circ_0089153/hsa-miR-608 binding sponge was validated. Downstream gene interaction networks showed that EGFR and p53 had the strongest co-expression. In vitro transfection results confirmed the suppressive function of miR-608 and EGFR p53. Hsa_circ_0089153/hsa-miR-608/EGFR p53 interaction pathway enrichment analysis confirmed functions mainly enriched in MAPK and related signaling pathways regulating AB progression. CONCLUSIONS Six novel circRNAs were identified. Hsa_circ_0089153/hsa-miR-608 sponging was validated, hsa-miR-608 downregulated EGFR and p53, which might further regulate cell proliferation, differentiation, apoptosis, and cell cycle processes via the MAPK signaling pathway.
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Affiliation(s)
- Jinwen Liu
- Department of Periodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, China.,Department of Oral Histopathology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China
| | - Xue Qiao
- Department of Oral Histopathology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China.,Central Laboratory Department, School and Hospital of Stomatology, Liaoning Province Key Laboratory of Oral Disease, China Medical University, Shenyang, China
| | - Jiayi Liu
- Department of Oral Histopathology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China
| | - Ming Zhong
- Department of Oral Histopathology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China.,Department of Stomatology, Xiang'an Hospital of Xiamen University, Xiamen, China
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30
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Wang S, Zhang K, Tan S, Xin J, Yuan Q, Xu H, Xu X, Liang Q, Christiani DC, Wang M, Liu L, Du M. Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies. Mol Cancer 2021; 20:13. [PMID: 33430880 PMCID: PMC7798340 DOI: 10.1186/s12943-020-01298-z] [Citation(s) in RCA: 196] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 12/21/2020] [Indexed: 02/08/2023] Open
Abstract
Cancer is a leading cause of death worldwide, particularly because of its high mortality rate in patients who are diagnosed at late stages. Conventional biomarkers originating from blood are widely used for cancer diagnosis, but their low sensitivity and specificity limit their widespread application in cancer screening among the general population. Currently, emerging studies are exploiting novel, highly-accurate biomarkers in human body fluids that are obtainable through minimally invasive techniques, which is defined as liquid biopsy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs generated mainly by pre-mRNA splicing. Following the rapid development of high-throughput transcriptome analysis techniques, numerous circRNAs have been recognized to exist stably and at high levels in body fluids, including plasma, serum, exosomes, and urine. CircRNA expression patterns exhibit distinctly differences between patients with cancer and healthy controls, suggesting that circRNAs in body fluids potentially represent novel biomarkers for monitoring cancer development and progression. In this study, we summarized the expression of circRNAs in body fluids in a pan-cancer dataset and characterized their clinical applications in liquid biopsy for cancer diagnosis and prognosis. In addition, a user-friendly web interface was developed to visualize each circRNA in fluids (https://mulongdu.shinyapps.io/circrnas_in_fluids/).
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Affiliation(s)
- Sumeng Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Ke Zhang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Shanyue Tan
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Junyi Xin
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Centre for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China
| | - Qianyu Yuan
- Departments of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA
| | - Huanhuan Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Xian Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Qi Liang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China
| | - David C Christiani
- Departments of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.,Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Meilin Wang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, People's Republic of China. .,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Centre for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China.
| | - Lingxiang Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China.
| | - Mulong Du
- Department of Biostatistics, Centre for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China.
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31
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Duan L, Liang Y, Xu X, Wang J, Li X, Sun D, Deng Z, Li W, Wang D. Noncoding RNAs in subchondral bone osteoclast function and their therapeutic potential for osteoarthritis. Arthritis Res Ther 2020; 22:279. [PMID: 33239099 PMCID: PMC7690185 DOI: 10.1186/s13075-020-02374-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 11/13/2020] [Indexed: 02/08/2023] Open
Abstract
Osteoclasts are the only cells that perform bone resorption. Noncoding RNAs (ncRNAs) are crucial epigenetic regulators of osteoclast biological behaviors ranging from osteoclast differentiation to bone resorption. The main ncRNAs, including miRNAs, circRNAs, and lncRNAs, compose an intricate network that influences gene transcription processes related to osteoclast biological activity. Accumulating evidence suggests that abnormal osteoclast activity leads to the disturbance of subchondral bone remodeling, thus initiating osteoarthritis (OA), a prevalent joint disease characterized mainly by cartilage degradation and subchondral bone remodeling imbalance. In this review, we delineate three types of ncRNAs and discuss their related complex molecular signaling pathways associated with osteoclast function during bone resorption. We specifically focused on the involvement of noncoding RNAs in subchondral bone remodeling, which participate in the degradation of the osteochondral unit during OA progression. We also discussed exosomes as ncRNA carriers during the bone remodeling process. A better understanding of the roles of ncRNAs in osteoclast biological behaviors will contribute to the treatment of bone resorption-related skeletal diseases such as OA.
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Affiliation(s)
- Li Duan
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.
| | - Yujie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen Key Laboratory for Psychological Healthcare & Shenzhen Institute of Mental Health, Shenzhen, 518003, China
| | - Xiao Xu
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Jifeng Wang
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Xingfu Li
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Deshun Sun
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Zhiqin Deng
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China
| | - Wencui Li
- Hand and Foot Surgery Department, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong, China
| | - Daping Wang
- Department of Orthopaedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China. .,Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.
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Circular RNAs are a novel type of non-coding RNAs in ROS regulation, cardiovascular metabolic inflammations and cancers. Pharmacol Ther 2020; 220:107715. [PMID: 33141028 DOI: 10.1016/j.pharmthera.2020.107715] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/19/2020] [Indexed: 02/06/2023]
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed back-splicing. Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, and often exhibit cell-specific, and tissue-specific/developmental-stage-specific expression and can be largely independent of the expression levels of the linear host gene-encoded linear RNAs; 2) the biogenesis of circRNAs via back-splicing is different from the canonical splicing of linear RNAs; 3) circRNA biogenesis is regulated by specific cis-acting elements and trans-acting factors; 4) circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RNA-binding protein (RBP), regulators of splicing and transcription, modifiers of parental gene expression, and regulators of protein translation or being translated into peptides in various diseases; 5) circRNAs have been identified for their enrichment and stability in exosomes and detected in body fluids such as human blood, saliva, and cerebrospinal fluids, suggesting that these exo-circRNAs have potential applications as disease biomarkers and novel therapeutic targets; 6) several circRNAs are regulated by oxidative stress and mediate reactive oxygen species (ROS) production as well as promote ROS-induced cellular death, cell apoptosis, and inflammation; 7) circRNAs have also emerged as important regulators in atherosclerotic cardiovascular disease, metabolic disease, and cancers; 8) the potential mechanisms of several circRNAs have been described in diseases, hinting at their potential applications as novel therapeutic targets. In this highlight, we summarized the current understandings of the biogenesis and functions of circRNAs and their roles in ROS regulation and vascular inflammation-associated with cardiovascular and metabolic disease. (Word count: 272).
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Bai M, Fu W, Su G, Cao J, Gao L, Huang C, Ma H, Zhang J, Yue P, Bai B, Lin Y, Meng W, Li X. The role of extracellular vesicles in cholangiocarcinoma. Cancer Cell Int 2020. [PMCID: PMC7709354 DOI: 10.1186/s12935-020-01526-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AbstractCholangiocarcinoma (CCA) is a rare tumor that arises from cholangiocytes, the epithelial cells of the bile duct. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis and high recurrence rate. Due to the lack of specific biomarkers, it is difficult to diagnose CCA early and evaluate prognosis. Extracellular vesicles (EVs), which include apoptotic bodies, microvesicles and exosomes, have emerged as having important roles in cell-to-cell communication in both normal physiology and pathological conditions. Some research has found that EVs play a crucial role in the occurrence and development of CCA. EVs can carry specific molecular substances such as nucleic acids and proteins, which have potential for the diagnosis and therapy of CCA. This article reviews the current knowledge on the role of EVs in CCA. We highlight EVs and their functions in the physiology and pathophysiology of CCA, and discuss their therapeutic potential and their role as biomarkers.
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Yang M, Huang W. Circular RNAs in nasopharyngeal carcinoma. Clin Chim Acta 2020; 508:240-248. [PMID: 32417214 DOI: 10.1016/j.cca.2020.05.029] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/13/2020] [Accepted: 05/13/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) is a geographical distributed epithelial tumor of head and neck, which is prevalent in east Africa and Asia, especially southern China. Moreover, NPC has an unfavorable clinical effect and is prone to metastasis at an advanced stage. Although the recovery rate of patients has been improved due to concurrent chemoradiotherapy, poor curative effects and low overall survival remain key issues. The precise mechanisms and pivotal regulators of NPC remain still unclear. To improve the therapeutic efficacy, we focused on related-NPC circular RNAs (circRNAs). CircRNAs are a unique type of endogenous non-coding RNAs (ncRNAs) with a covalent closed-loop structure. Their expression is rich, stable and conservative. Different circRNA have specific tissue and developmental stages and can be detected in body fluids. In addition, circRNAs are involved in multiple pathological processes, especially in cancers. In recent years, using high-throughput indicator technology and bioinformatics technology, a large number of circRNAs have been identified in NPC cells and verified to have biological functions and mechanisms of action. This article aims to provide a retrospective review of the latest research on the proliferation and migration of related-NPC circRNA. Specifically, we focused on the roles and mechanisms of circRNAs in the development and progression of NPC. CONCLUSION CircRNA can act as an oncogene or tumor suppressor gene and participate in NPC progression (e.g., proliferation, apoptosis, migration, and invasion). In short, circRNAs have potential as biomarkers for the diagnosis, prognosis and treatment of NPC.
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Affiliation(s)
- Mingxiu Yang
- Cancer Research Institute, Hengyang Medical College of University of South China, Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology (2016TP1015), Hengyang, Hunan Province, People's Republic of China
| | - Weiguo Huang
- Cancer Research Institute, Hengyang Medical College of University of South China, Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology (2016TP1015), Hengyang, Hunan Province, People's Republic of China.
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