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      Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/β-catenin signaling pathway

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          Abstract

          CircRNA is a novel type of RNA molecule formed by a covalently closed loop which have no 5′-3′ polarity and possess no polyA tail and relatively stable due to the cyclic structure. Therefore, they may serve as potential targets and diagnosis biomarkers for tumor therapy. cZNF292 is an important circular oncogenic RNA and plays a critical role in the progression of tube formation. This study is aimed at exploring the role of cZNF292 in human glioma tube formation and its potential mechanism of action. We found that cZNF292 silencing suppresses tube formation by inhibiting glioma cell proliferation and cell cycle progression. Cell cycle progression in human glioma U87MG and U251 cells was halted at S/G2/M phase via the Wnt/β-catenin signaling pathway and related genes such as PRR11, Cyclin A, p-CDK2, VEGFR-1/2, p-VEGFR-1/2 and EGFR. The results suggest that cZNF292 silencing plays an important role in the tube formation process and has potential for application as a therapeutic target and biomarker in glioma.

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          Most cited references11

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          Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2

          Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include circular RNAs, which include exonic circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ-Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a ternary complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 ternary complex arrested the function of CDK2 and blocked cell cycle progression.
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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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              Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA.

              Circular RNAs (circRNAs) are noncoding RNAs generated by back splicing. Back splicing has been considered a rare event, but recent studies suggest that circRNAs are widely expressed. However, the expression, regulation, and function of circRNAs in vascular cells is still unknown.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                27 September 2016
                23 August 2016
                : 7
                : 39
                : 63449-63455
                Affiliations
                1 Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, China
                2 Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, China
                3 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
                4 Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, GA, USA
                5 School of Pharmacal Sciences, Tianjin Medical University, Tianjin, China
                6 Department of Genetics, College of Basic Medicine, Tianjin Medical University, Tianjin, China
                Author notes
                Article
                11523
                10.18632/oncotarget.11523
                5325376
                27613831
                edfb07f4-c2ff-4675-aea2-0becf7964335
                Copyright: © 2016 Yang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 April 2016
                : 11 August 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                circular rnas,cznf292,glioma,tube formation,proliferation
                Oncology & Radiotherapy
                circular rnas, cznf292, glioma, tube formation, proliferation

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