title: MicroRNA-381 suppresses cell growth and invasion by targeting the liver receptor homolog-1 in hepatocellular carcinoma.
abstract: MicroRNAs (miRs) have emerged as prospective tools for human cancer therapy, including hepatocellular carcinoma (HCC) therapy. Previous studies have suggested that miR-381 functions as oncogenic or tumor-suppressive miRs in other cancer types. However, the role of miR-381 in HCC remains unknown. The present study investigated the expression and functional role of miR-381 in HCC. miR-381 expression was significantly decreased in HCC tissues and cell lines. miR-381 overexpression significantly inhibited HCC cell proliferation and colony formation, induced G0/G1 cell cycle arrest and suppressed cell invasion. Conversely, suppression of miR-381 showed the opposite effect in HCC cells. Bioinformatics analysis and dual-luciferase reporter assay results showed that miR-381 directly targeted the 3'-untranslated region of liver receptor homolog-1 (LRH-1), and quantitative polymerase chain reaction and western blot analysis results showed that miR-381 negatively modulated LRH-1 expression. Data elucidated that miR-381 directly regulated HCC cell growth and invasion, as well as the Wnt signaling pathways, by targeting LRH-1. Clinical tissue detection data revealed an inverse correlation between miR-381 and LRH-1 expression in HCC tissues, further indicating the functional significance of miR-381-LRH-1 in regulating HCC tumorigenesis. The present study indicates that miR-381 may be a novel tumor suppressor that blocks HCC growth and invasion by targeting LRH-1. The results present novel insights into understanding the molecular mechanism underlying HCC tumorigenesis and provide a future direction to the development of therapeutic interventions for HCC.
authors.affiliation: Department of Hepatobiliary and Pancreatic Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Intensive Care Unit, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.
authors.forename: Shixing
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Pancreatic Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Hepatobiliary and Pancreatic Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Baorong
authors.initials: B
authors.lastname: Chi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C588249:MIRN381 microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear