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      Circular RNAs as novel biomarkers with regulatory potency in human diseases

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      Future Science OA
      Future Science Ltd
      biomarkers, characterization, circRNAs, function, human disease, regulators

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          Circular RNAs (circRNAs) are a large class of noncoding RNAs characterized with closed loop structures without 3′ and 5′ polar ends. They can roughly be divided into exonic circRNAs, exon–intron circRNAs and circular intronic RNAs. CircRNAs are characterized with stability, prevalence, specificity and conservation, which arouse great interest in circRNAs as disease biomarkers. Their abilities to sponge to miRNAs, cis-regulate parent genes, bind to proteins and encode proteins endow circRNAs a critical role of regulation in eukaryotic cells. This concise review focuses on circRNAs as functional biomarkers and therapeutic targets in both tumor and nontumorous diseases.

          Lay abstract

          Although they were discovered in 1970s, circular RNAs (circRNAs) have attracted great interest only relatively recently. Instead of genome ‘junk matters’, circRNAs are now considered as promising biomarkers and treatment targets. CircRNAs are involved in numerous cancer-related and noncancer diseases, such as lung cancer, gastric cancer, cardiovascular diseases, diabetes mellitus and so on. This review outlines the classification, characterization and function of circRNAs, with a specific focus on recent studies concerning the role of circRNAs in human diseases.

          Most cited references50

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          Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation.

          Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate >2,500 fruit fly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and the circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor >1,000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs and note their preferred derivation from neural genes and enhanced accumulation in neural tissues. Interestingly, circular isoforms increase substantially relative to linear isoforms during CNS aging and constitute an aging biomarker. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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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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              Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

              The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus.

                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                July 2018
                23 May 2018
                : 4
                : 7
                : FSO314
                [1 ]The MOH Key Laboratory of Geriatrics, National Center of Gerontology, Beijing Hospital, 1 Dahua Road, DongCheng District, Beijing, PR China
                Author notes
                *Author for correspondence: fsz252@ 123456163.com
                © 2018 Yuan Fang

                This work is licensed under a Creative Commons Attribution 4.0 License

                : 02 April 2018
                : 08 May 2018
                : 23 May 2018

                biomarkers,characterization,circrnas,function,human disease,regulators


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