Wei Ding1,2,1, Hongbo Tan3,1, Xuemei Li1, Yue Zhang1, Fang Fang2, Yuanyuan Tian1, Jin Li1, Xinghua Pan4. 1. Department of Clinical Laboratory, Kunming General Hospital, Chinese People's Liberation Army, Kunming 650032, Yunnan, China. 2. College of Medicine, Yunnan Economic Management College, Kunming 650106, Yunnan, China. 3. Department of Orthopedics, Kunming General Hospital of Chinese People's Liberation Army, Kunming 650032, Yunnan, China. 4. Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital, Chinese People's Liberation Army, Kunming 650032, Yunnan, China.
Abstract
BACKGROUNDS: MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3'-untranslated region (3'-UTR) of target mRNA molecules. The aim of the study is to investigate the clinical role and functional effects of microRNA-493 (miR-493) in human hepatocellular carcinoma (HCC). METHODS: Expression of miR-493 in 58 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity was evaluated by CCK8 assay and trans-well invasion assay. Luciferase reporter assay, western blot and qRT-PCR were used to detect the association between miR-493 expression and zinc finger protein X-linked (ZFX) in HCC. RESULTS: Expression of miR-493 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Lower miR-493 expression associated with tumor size, vascular invasion and poor overall survival (OS) and disease free survival (DFS) time of HCC patients. In vitro, transfection of miR-493 mimic in HCC cells inhibited cell proliferation and invasion abilities. However, transfection of miR-493 inhibitor in HCC cells had promoting effects. Luciferase reporter assay, qRT-PCR and western blot analysis demonstrated that miR-493 targeting 3'-untranslated region (3'-UTR) of ZFX and overexpression of miR-493 inhibited its expression. Moreover, enforced ZFX expression rescued the effects of miR-493 mimic on cell proliferation and invasion. CONCLUSION: MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment.
BACKGROUNDS: MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3'-untranslated region (3'-UTR) of target mRNA molecules. The aim of the study is to investigate the clinical role and functional effects of microRNA-493 (miR-493) in humanhepatocellular carcinoma (HCC). METHODS: Expression of miR-493 in 58 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity was evaluated by CCK8 assay and trans-well invasion assay. Luciferase reporter assay, western blot and qRT-PCR were used to detect the association between miR-493 expression and zinc finger protein X-linked (ZFX) in HCC. RESULTS: Expression of miR-493 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Lower miR-493 expression associated with tumor size, vascular invasion and poor overall survival (OS) and disease free survival (DFS) time of HCCpatients. In vitro, transfection of miR-493 mimic in HCC cells inhibited cell proliferation and invasion abilities. However, transfection of miR-493 inhibitor in HCC cells had promoting effects. Luciferase reporter assay, qRT-PCR and western blot analysis demonstrated that miR-493 targeting 3'-untranslated region (3'-UTR) of ZFX and overexpression of miR-493 inhibited its expression. Moreover, enforced ZFX expression rescued the effects of miR-493 mimic on cell proliferation and invasion. CONCLUSION:MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment.
Authors: Jian Jin; Banrida Wahlang; Hongxue Shi; Josiah E Hardesty; K Cameron Falkner; Kimberly Z Head; Sudhir Srivastava; Michael L Merchant; Shesh N Rai; Matthew C Cave; Russell A Prough Journal: Med Chem Res Date: 2020-06-07 Impact factor: 1.965