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      Current Understanding of Circular RNAs in Gastric Cancer

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          Abstract

          Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Advanced diagnosis and high rates of relapse and metastasis are associated with the poor prognosis of this disease. GC has a complex etiopathogenesis of which the underlying mechanisms remain to be explored. Studies on circular RNAs (circRNAs), noncoding RNAs that may be potential targets in GC, have made substantial progress over the past few years. CircRNAs exert important effects on the onset and progression of GC. Hence, this article aims to summarize the findings of recent studies of circRNAs related to GC and to describe the underlying mechanisms and potential applications. The findings indicate that circRNAs participate in GC regulation, proliferation, invasion, and metastasis through regulating microRNAs, proteins, genes, and signaling pathways. In addition, dysregulated circRNAs may be used as novel diagnostic and prognostic biomarkers or therapeutic targets. This review is expected to facilitate a better understanding of GC, and it suggests novel circRNA-based methods to inhibit or prevent GC.

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          Most cited references41

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          Overview of microRNA biology.

          In considering an overview of microRNA biology, it is useful to consider microRNAs as a part of cellular communication. At the simplest level, microRNAs act to decrease the expression of messenger RNAs that contain stretches of sequence complementary to the microRNA. This function can be likened to the function of endogenous or synthetic short interfering RNA. However, microRNA function is more complicated and nuanced than this "on-off" model would suggest. Further, many microRNA targets are themselves noncoding RNAs. In this review, the authors discuss the role of microRNAs in shaping the proteome of the cell in a way that is consistent with microRNA involvement in a highly regulated conversation, sensitive to outside influence and internal feedback.
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            An emerging function of circRNA-miRNAs-mRNA axis in human diseases

            Circular RNAs (circRNAs), a novel class of long noncoding RNAs, are characterized by a covalently closed continuous loop without 5′ or 3′ polarities structure and have been widely found in thousands of lives including plants, animals and human beings. Utilizing the high-throughput RNA sequencing (RNA-seq) technology, recent findings have indicated thata great deal of circRNAs, which are endogenous, stable, widely expressed in mammalian cells, often exhibit cell type-specific, tissue-specific or developmental-stage-specific expression. Evidences are arising that some circRNAs might regulate microRNA (miRNA) function as microRNA sponges and play a significant role in transcriptional control. circRNAs associate with related miRNAs and the circRNA-miRNA axes are involved in a serious of disease pathways such as apoptosis, vascularization, invasion and metastasis. In this review, we generalize and analyse the aspects including synthesis, characteristics, classification, and several regulatory functions of circRNAs and highlight the association between circRNAs dysregulation by circRNA-miRNA-mRNA axis and sorts of diseases including cancer- related and non-cancer diseases.”
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              A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer.

              In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                CMAR
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                13 December 2019
                2019
                : 11
                : 10509-10521
                Affiliations
                [1 ]Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University , Changchun, Jilin, People’s Republic of China
                Author notes
                Correspondence: Jingjing Liu Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University , Changchun, Jilin130041, People’s Republic of ChinaTel +86-431-81136210 Email jingjingstarone@163.com
                Author information
                http://orcid.org/0000-0001-9526-6984
                http://orcid.org/0000-0002-5095-8466
                Article
                223204
                10.2147/CMAR.S223204
                6916696
                31853202
                b54f562b-9cf4-49a3-a9d9-caff07bf282a
                © 2019 Tang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 July 2019
                : 15 November 2019
                Page count
                Figures: 1, Tables: 4, References: 101, Pages: 13
                Categories
                Review

                Oncology & Radiotherapy
                gastric cancer,circular rna,biomarkers,diagnosis,prognosis
                Oncology & Radiotherapy
                gastric cancer, circular rna, biomarkers, diagnosis, prognosis

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