title: MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells.
abstract: The replication and infectivity of the lipotropic hepatitis C virus (HCV) are regulated by cellular lipid status. Among differentially expressed microRNAs (miRNAs), we found that miR-27a was preferentially expressed in HCV-infected liver over hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcription factor RXRα and the lipid transporter ATP-binding cassette subfamily A member 1. In addition, miR-27a repressed the expression of many lipid metabolism-related genes, including FASN, SREBP1, SREBP2, PPARα, and PPARγ, as well as ApoA1, ApoB100, and ApoE3, which are essential for the production of infectious viral particles. miR-27a repression increased the cellular lipid content, decreased the buoyant density of HCV particles from 1.13 to 1.08 g/cm(3), and increased viral replication and infectivity. miR-27a overexpression substantially decreased viral infectivity. Furthermore, miR-27a enhanced in vitro interferon (IFN) signaling, and patients who expressed high levels of miR-27a in the liver showed a more favorable response to pegylated IFN and ribavirin combination therapy. Interestingly, the expression of miR-27a was upregulated by HCV infection and lipid overload through the adipocyte differentiation transcription factor C/EBPα. In turn, upregulated miR-27a repressed HCV infection and lipid storage in cells. Thus, this negative feedback mechanism might contribute to the maintenance of a low viral load and would be beneficial to the virus by allowing it to escape host immune surveillance and establish a persistent chronic HCV infection.
authors: Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors: Takayoshi
authors: T
authors: Shirasaki
authors: Masao
authors: M
authors: Honda
authors: Tetsuro
authors: T
authors: Shimakami
authors: Rika
authors: R
authors: Horii
authors: Taro
authors: T
authors: Yamashita
authors: Yoshio
authors: Y
authors: Sakai
authors: Akito
authors: A
authors: Sakai
authors: Hikari
authors: H
authors: Okada
authors: Risa
authors: R
authors: Watanabe
authors: Seishi
authors: S
authors: Murakami
authors: MinKyung
authors: M
authors: Yi
authors: Stanley M
authors: SM
authors: Lemon
authors: Shuichi
authors: S
authors: Kaneko
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D015536:Down-Regulation; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs