title: MicroRNA-185 induces potent autophagy via AKT signaling in hepatocellular carcinoma.
abstract: Studies have demonstrated that microRNA 185 may be a promising therapeutic target in liver cancer. However, its role in hepatocellular carcinoma is largely unknown. In this study, the proliferation of human HepG2 cells was inhibited by transfection of microRNA 185 mimics. Cell-cycle analysis revealed arrest at the G0/G1 phase. Transfection of HepG2 cells with microRNA 185 mimics significantly induced apoptosis. These data confirmed microRNA 185 as a potent cancer suppressor. We demonstrated that microRNA 185 was a compelling inducer of autophagy, for the first time. When cell autophagy was inhibited by chloroquine or 3-methyladenine, microRNA 185 induced more cell apoptosis. MicroRNA 185 acted as a cancer suppressor by regulating AKT1 expression and phosphorylation. Dual-luciferase reporter assays indicated that microRNA 185 suppressed the expression of target genes including RHEB, RICTOR, and AKT1 by directly interacting with their 3'-untranslated regions. Binding site mutations eliminated microRNA 185 responsiveness. Our findings demonstrate a new role of microRNA 185 as a key regulator of hepatocellular carcinoma via autophagy by dysregulation of AKT1 pathway.
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.|3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Shenghu
authors.initials: S
authors.lastname: Feng
authors.affiliation: 4 Division of Infectious Disease, Civil Aviation General Hospital, Beijing, China.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Liang
authors.affiliation: 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.|3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Li
authors.affiliation: 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.|3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.|3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Lu
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.|3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D001343:Autophagy / Q000235:genetics; D040761:Biomimetic Materials / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D035683:MicroRNAs / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection / Q000379:methods
chemical_list: C552431:MIRN185 microRNA, human; D035683:MicroRNAs; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1; Apoptosis; autophagy; cell-cycle arrest; microRNA 185