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      Circular RNA cMTO1 Promotes PTEN Expression Through Sponging miR-181b-5p in Liver Fibrosis

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          Abstract

          Background

          Circular RNAs (circRNAs) are considered as key regulators of cancer biology. Recently, cMTO1 (a circRNA derived from MTO1 gene, hsa_circ_0007874) has been demonstrated to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the roles of cMTO1 in liver fibrosis are largely unknown.

          Methods

          Expressions and roles of cMTO1 were examined in vivo and in vitro during liver fibrosis. The interaction between microRNA-181b-5p (miR-181b-5p) and cMTO1 was analyzed by luciferase activity assays and pull down assays.

          Results

          cMTO1 was shown to be reduced in the liver from patients with cirrhosis. In addition, cMTO1 was down-regulated in the mouse fibrotic livers as well as activated hepatic stellate cells (HSCs). Restoring of cMTO1 led to a reduction in HSC proliferation. Results of immunofluorescence analysis showed that cMTO1 suppressed the expressions of α-SMA and type I collagen. cMTO1 was found to be expressed in the cytoplasm of HSCs. Further studies confirmed that cMTO1 and miR-181b-5p were co-located in the cytoplasm. Interestingly, there was an interaction between cMTO1 and miR-181b-5p. Results of luciferase reporter assays and pull down assays confirmed that miR-181b-5p could bind to cMTO1. cMTO1-inhibited HSC activation was blocked down by miR-181b-5p or PTEN. Meanwhile, PTEN was a target of miR-181b-5p.

          Conclusion

          cMTO1 inhibits HSC activation, at least in part, through miR-181b-5p-mediated PTEN expression. Our results also suggest that cMTO1 may be a novel therapeutic target in liver fibrosis.

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          Most cited references19

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          Circular RNAs: splicing's enigma variations.

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            The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.

            Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years.
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              CRISPR/Cas13a‐Powered Electrochemical Microfluidic Biosensor for Nucleic Acid Amplification‐Free miRNA Diagnostics

              Noncoding small RNAs, such as microRNAs, are becoming the biomarkers of choice for multiple diseases in clinical diagnostics. A dysregulation of these microRNAs can be associated with many different diseases, such as cancer, dementia, and cardiovascular conditions. The key for effective treatment is an accurate initial diagnosis at an early stage, improving the patient's survival chances. In this work, the first clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a-powered microfluidic, integrated electrochemical biosensor for the on-site detection of microRNAs is introduced. Through this unique combination, the quantification of the potential tumor markers microRNA miR-19b and miR-20a is realized without any nucleic acid amplification. With a readout time of 9 min and an overall process time of less than 4 h, a limit of detection of 10 pm is achieved, using a measuring volume of less than 0.6 µL. Furthermore, the feasibility of the biosensor platform to detect miR-19b in serum samples of children, suffering from brain cancer, is demonstrated. The validation of the obtained results with a standard quantitative real-time polymerase chain reaction method shows the ability of the electrochemical CRISPR-powered system to be a low-cost, easily scalable, and target amplification-free tool for nucleic acid based diagnostics.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                31 July 2020
                2020
                : 8
                : 714
                Affiliations
                [1] 1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, China
                [2] 2Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, China
                [3] 3Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, China
                [4] 4Department of Laboratory Medicine, Lishui Municipal Central Hospital , Lishui, China
                Author notes

                Edited by: Eiman Aleem, University of Arizona, United States

                Reviewed by: Zhong Qiu Lu, The First Affiliated Hospital of Wenzhou Medical University, China; Linyong Du, University of Texas MD Anderson Cancer Center, United States

                *Correspondence: Jianjian Zheng, 120378196@ 123456qq.com

                These authors have contributed equally to this work

                This article was submitted to Cell Growth and Division, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00714
                7413143
                32850833
                f5e1f60e-2194-4076-9eea-1fc2552eada5
                Copyright © 2020 Jin, Li, Dong, Huang, Yu and Zheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 January 2020
                : 13 July 2020
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 35, Pages: 12, Words: 0
                Categories
                Cell and Developmental Biology
                Original Research

                cmto1,mir-181b-5p,liver fibrosis,hepatic stellate cell,pten
                cmto1, mir-181b-5p, liver fibrosis, hepatic stellate cell, pten

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