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      Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p

      research-article
      ,
      Cancer Cell International
      BioMed Central
      Glioma, circ_0000020, miR-142-5p, PIK3CA

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          Abstract

          Background

          Multiple circular RNAs (circRNAs) have been recently described as crucial oncogenic factors or tumor suppressors. This study aimed to investigate the role of circ_0000020 in glioma progression.

          Methods

          Circ_0000020 and miR-142-5p expressions in glioma samples were assessed through qRT-PCR, and then the association between pathological indexes and circ_0000020 expressions was analyzed. Functional experiment was performed with human glioma cell lines U251 and U87. Gain-of-function and loss-of-function models were established. CCK-8 assay was used to detect glioma cell proliferation. Transwell assay was used to examine glioma cell migration and invasion. The regulatory relationships among circ_0000020, miR-142-5p and phosphatidylinositol 3-kinase C (PIK3CA) were investigated by bioinformatics analysis, luciferase reporter assay, qRT-PCR and Western blot. In vivo tumorigenesis assay was performed with nude mice to further validate the demonstrations of in vitro experiments.

          Results

          Circ_0000020 expression in glioma samples was remarkably increased compared with that in normal brain tissues and its high expression was associated with unfavorable pathological indexes. Circ_0000020 overexpression remarkably accelerated proliferation, migration and invasion of glioma cells. Accordingly, circ_0000020 knockdown suppressed the malignant phenotypes of glioma cells. Circ_0000020 overexpression significantly reduced miR-142-5p expression by sponging it, and circ_0000020 could enhance the expression of PIK3CA, which was a target gene of miR-142-5p.

          Conclusions

          Circ_0000020 promotes glioma progression via miR-142-5p/PIK3CA axis.

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          Most cited references48

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          Exon-intron circular RNAs regulate transcription in the nucleus.

          Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression. A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells. Here, we report a class of circRNAs associated with RNA polymerase II in human cells. In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs. EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes. Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs.
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            Regulation of circRNA biogenesis.

            Unlike linear RNAs terminated with 5' caps and 3' tails, circular RNAs are characterized by covalently closed loop structures with neither 5' to 3' polarity nor polyadenylated tail. This intrinsic characteristic has led to the general under-estimation of the existence of circular RNAs in previous polyadenylated transcriptome analyses. With the advent of specific biochemical and computational approaches, a large number of circular RNAs from back-spliced exons (circRNAs) have been identified in various cell lines and across different species. Recent studies have uncovered that back-splicing requires canonical spliceosomal machinery and can be facilitated by both complementary sequences and specific protein factors. In this review, we highlight our current understanding of the regulation of circRNA biogenesis, including both the competition between splicing and back-splicing and the previously under-appreciated alternative circularization.
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              Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types

              Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.
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                Author and article information

                Contributors
                yexiebu5258881@163.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                28 January 2021
                28 January 2021
                2021
                : 21
                : 79
                Affiliations
                GRID grid.452911.a, ISNI 0000 0004 1799 0637, Department of Neurosurgery, , Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, ; Jingzhou Street No. 136, Xiangyang, 441021 Hubei China
                Author information
                http://orcid.org/0000-0002-2110-6598
                Article
                1767
                10.1186/s12935-021-01767-5
                7841906
                33509213
                b444fafd-118f-4ffb-bfa7-e35829d6ce0f
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 13 February 2020
                : 10 January 2021
                Categories
                Primary Research
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                glioma,circ_0000020,mir-142-5p,pik3ca
                Oncology & Radiotherapy
                glioma, circ_0000020, mir-142-5p, pik3ca

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