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      Circular RNA midline-1 (circMID1) promotes proliferation, migration, invasion and glycolysis in prostate cancer

      research-article
      a , b , a
      Bioengineered
      Taylor & Francis
      Prostate cancer, circMID1, miR-330-3p

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          ABSTRACT

          The key role of circular RNA (circRNA) in the malignant progression of cancers has been demonstrated. However, the role of circRNA midline-1 (circMID1) in prostate cancer (PCa) progression has not been clarified. Quantitative real-time PCR was used to measure relative expression. Function analysis was performed using EdU staining, colony formation assay, flow cytometry, wound healing assay, transwell assay and cell glycolysis detection. The protein levels were detected by Western blot analysis. RNA pull-down assay, dual-luciferase reporter assay and RIP assay were performed to verify RNA interaction. Animal experiments were utilized to explore the effects of circMID1 knockdown on PCa tumorigenesis in vivo. Our results showed that circMID1 was upregulated in PCa tissues and cells and its knockdown inhibited PCa cell proliferation, migration, invasion and glycolysis in vitro, as well as PCa tumorigenesis in vivo. IGF1R and YTHDC2 were highly expressed in PCa tissues and cells, and their expression was positively regulated by circMID1. IGF1R and YTHDC2 overexpression reversed the inhibitory effect of circMID1 silencing on PCa cell progression. In terms of mechanism, circMID1 could sponge miR-330-3p and miR-330-3p could target IGF1R and YTHDC2. Functional experiments showed that circMID1 sponged miR-330-3p to regulate PCa progression via the YTHDC2/IGF1R/AKT axis. In conclusion, our data confirmed that circMID1 might play a pro-cancer role in PCa, which promoted PCa progression through regulating the miR-330-3p/YTHDC2/IGF1R/AKT axis.

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          Most cited references38

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          Natural RNA circles function as efficient microRNA sponges.

          MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
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            The biogenesis, biology and characterization of circular RNAs

            Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
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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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                Author and article information

                Journal
                Bioengineered
                Bioengineered
                Bioengineered
                Taylor & Francis
                2165-5979
                2165-5987
                25 February 2022
                2022
                25 February 2022
                : 13
                : 3
                : 6293-6308
                Affiliations
                [a ]Department of Uropoiesis Surgical, The First Affiliated Hospital of Zhengzhou University; , Zhengzhou City, Henan Province, China
                [b ]Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University; , Zhengzhou City, Henan Province, China
                Author notes
                CONTACT Jinjian Yang dxtq0604@ 123456126.com Jianshe East Road, Zhengzhou City, Henan Province 450052, China
                Article
                2037367
                10.1080/21655979.2022.2037367
                8973952
                35212614
                5a5a8ab3-f4a5-4af3-98e5-2a20e17b2b87
                © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 7, Tables: 2, References: 38, Pages: 15
                Categories
                Research Article
                Research Paper

                Biomedical engineering
                prostate cancer,circmid1,mir-330-3p
                Biomedical engineering
                prostate cancer, circmid1, mir-330-3p

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