title: Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway.
abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishida
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hosui
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kodama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Hayato
authors.initials: H
authors.lastname: Hikita
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000821:virology*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014779:Virus Replication
chemical_list: C551410:MIRN491 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt