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      Profiling and bioinformatics analyses of differential circular RNA expression in prostate cancer cells

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          Abstract

          Aim:

          There is little knowledge about the expression profile and function of circular RNAs (circRNAs) in prostate cancer (PCa).

          Methods:

          The expression profiles of circRNAs in RWPE-1, 22RV1 and PC3 cells were explored via high-throughput circRNAs sequencing and validated by real-time qPCR. The roles of differentially expressed circRNAs were evaluated by bioinformatics analyses.

          Results:

          Altogether 9545 circRNAs were identified and hundreds of differentially expressed circRNAs were recognized. CircRNA–miRNA networks analysis showed that many circRNAs, including circSLC7A6, circGUCY1A2 and circZFP57 could cross-talk with tumor-related miRNAs such as miR-21, miR-143 and miR-200 family.

          Conclusion:

          The results of our bioinformatics analyses suggested that circRNAs should play critical roles in the development and progression of PCa.

          Lay abstract

          The expression profile and role of circular RNAs (circRNAs) in prostate cancer (PCa) is unknown. In this study, the profiling of circRNAs in PCa cells was explored and their potential function was predicted by bioinformatics analyses. In total, 9545 circRNAs and hundreds of differentially expressed circRNAs were identified. Bioinformatics analyses showed that circRNAs including circSLC7A6, circGUCY1A2 and circZFP57 could cross talk with tumor-related miRNAs. This indicated that circRNAs might play an important role in PCa and warrant further study.

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          Most cited references28

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          CIRI: an efficient and unbiased algorithm for de novo circular RNA identification

          Recent studies reveal that circular RNAs (circRNAs) are a novel class of abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive detection of circRNAs from high-throughput transcriptome data is an initial and crucial step to study their biogenesis and function. Here, we present a novel chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately detect circRNAs from transcriptome data by employing multiple filtration strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time identify and experimentally validate the prevalence of intronic/intergenic circRNAs as well as fragments specific to them in the human transcriptome. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0571-3) contains supplementary material, which is available to authorized users.
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            The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells

            Among the identified thousands of circular RNAs (circRNA) in humans and animals, Cdr1as (also known as CiRS-7) was recently demonstrated to act as a powerful miR-7 sponge/inhibitor in developing midbrain of zebrafish, suggesting a novel mechanism for regulating microRNA functions. MiR-7 is abundantly expressed in islet cells, but overexpressing miR-7 in transgenic mouse β cells causes diabetes. Therefore, we infer that Cdr1as expression may inhibit miR-7 function in islet cells, which in turn improves insulin secretion. Here, we show the first characterization of Cdr1as expression in islet cells, which was upregulated by long-term forskolin and PMA stimulation, but not high glucose, indicating the involvement of cAMP and PKC pathways. Remarkably, both insulin content and secretion were significantly increased by overexpression of Cdr1as in islet cells. We further identified a new target Myrip in the Cdr1as/miR-7 pathway that regulates insulin granule secretion, and also another target Pax6 that enhances insulin transcription. Taken together, our findings revealed the effects of the strongly interacting pair of Cdr1as/miR-7 on insulin secretion, which may become a new target for improving β cell function in diabetes.
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              The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression

              Objectives Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis. Methods Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets. Results Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes. Conclusions Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.
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                Author and article information

                Journal
                Future Sci OA
                Future Sci OA
                FSOA
                Future Science OA
                Future Science Ltd (London, UK )
                2056-5623
                October 2018
                03 October 2018
                : 4
                : 9
                : FSOA340
                Affiliations
                [1 ]Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, PR China
                [2 ]Department of Urology, Lanzhou General Hospital of PLA, Lanzhou, PR China
                [3 ]Department of Histological Embryology, Second Military Medical University, Shanghai, PR China
                [4 ]Department of Cell Biology, Second Military Medical University, Shanghai, PR China
                Author notes
                *Author for correspondence: Tel./Fax: +86 021 3116 0006; sunyhsmmu@ 123456126.com
                **Author for correspondence: zi_xiaoyuan@ 123456163.com
                ***Author for correspondence: gaoxu.changhai@ 123456foxmail.com

                Authors contributed equally

                Article
                10.4155/fsoa-2018-0046
                6222276
                9c5afc01-e576-440f-8168-a6d981d6d632
                © 2018 Yinghao Sun

                This work is licensed under a Creative Commons Attribution 4.0 License

                History
                : 19 April 2018
                : 30 July 2018
                : 03 October 2018
                Categories
                Research Article

                bioinformatics analyses,circular rna,high-throughput sequencing,noncoding rna,prostate cancer

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