title: MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3.
abstract: The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3'-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC.
authors.affiliation: Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China; Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Lu
authors.forename: Xupeng
authors.initials: X
authors.lastname: Yue
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cui
authors.forename: Jufeng
authors.initials: J
authors.lastname: Zhang
authors.forename: KeWei
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Apoptosis; Hepatocellular carcinoma; Proliferation; STAT3; miR-124