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      Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma

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          Abstract

          Background

          Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained.

          Methods

          The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments.

          Results

          The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis.

          Conclusions

          ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.

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          Most cited references27

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          Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma

          Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer.
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            lncRNA involvement in hepatocellular carcinoma metastasis and prognosis

            Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide. Lack of proper molecular markers for diagnosis of HCC and treatment evaluation is a significant problem. Dysregulated expression of HCC-related lncRNAs such as MEG-3, MALAT1, HULC, HOTAIR, and H19 have been identified and closely related with tumorigenesis, metastasis, prognosis and diagnosis. In this review, we summarized recent highlighted functions and molecular mechanisms of the most extensively studied lncRNAs in the pathophysiology of hepatocellular carcinoma and their potential for serving as probable therapeutic targets.
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              Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p

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                Author and article information

                Contributors
                jinshi_1969@hotmail.com
                Journal
                J Exp Clin Cancer Res
                J. Exp. Clin. Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central (London )
                0392-9078
                1756-9966
                14 August 2020
                14 August 2020
                2020
                : 39
                : 159
                Affiliations
                [1 ]GRID grid.452435.1, Department of Laparoscopic Surgery, , the First Affiliated Hospital of Dalian Medical University, ; Dalian, 116000 Liaoning Province China
                [2 ]GRID grid.459742.9, ISNI 0000 0004 1798 5889, Department of thoracic surgery, , Cancer Hospital of China Medical University, Liaoning Cancer Hospital& Institute, ; Shenyang, 110042 Liaoning Province China
                [3 ]GRID grid.459742.9, ISNI 0000 0004 1798 5889, Department of Urological Surgery, , Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, ; Shenyang, 110042 Liaoning Province China
                [4 ]GRID grid.412636.4, Department of organ transplantation& hepatobiliary surgery, , the First Affiliated Hospital of China Medical University, ; Shenyang, 110042 Liaoning Province China
                [5 ]GRID grid.431010.7, Department of Gastrointestinal & Hernia & Bariatric Surgery, , the Third Xiangya Hospital of Central South University, ; Changsha, 410000 Hunan Province China
                Article
                1664
                10.1186/s13046-020-01664-1
                7427719
                32795316
                a219c2b3-eb55-4f07-8723-905dbf413728
                © The Author(s) 2020

                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
                : 18 February 2020
                : 4 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100010909, Young Scientists Fund;
                Award ID: 81702526
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100007765, Shenyang Science and Technology Bureau;
                Award ID: 1901210
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                lncrna zfpm2-as1,mir-139,liver hepatocellular carcinoma,tcga,bioinformatics analysis

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