title: Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1.
abstract: MicroRNAs (miRNAs) are highly conserved small noncoding RNAs participating in regulation of various cellular processes. Viruses have been shown to utilize cellular miRNAs to increase their replication in host cells. Until now, the role of miRNAs in hepatitis B virus (HBV) replication has remained largely unknown. In this study, a number of miRNA mimics were transfected into hepatoma cell lines with HBV replication. It was noted that microRNA-1 (miR-1) transfection resulted in a marked increase of HBV replication, accompanied with up-regulated HBV transcription, antigen expression, and progeny secretion. However, bioinformatics and luciferase reporter analysis suggested that miR-1 may not target the HBV genome directly but regulate the expression of host genes to enhance HBV replication. Further studies showed that miR-1 was able to enhance the HBV core promoter transcription activity by augmenting farnesoid X receptor α expression. In addition, miR-1 arrested the cell cycle at the G(1) phase and inhibited cell proliferation by targeting histone deacetylase 4 and E2F transcription factor 5. Analysis of the cellular gene expression profile indicated that miR-1 transfected hepatoma cells developed a differentiated phenotype of hepatocytes.
  
  
  CONCLUSIONS
  MiR-1 regulates the expression of several host genes to enhance HBV replication and reverse cancer cell phenotype, which is apparently beneficial for HBV replication. Our findings provide a novel perspective on the role of miRNAs in host-virus interactions in HBV infection.
authors.affiliation: Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.forename: Ejuan
authors.initials: E
authors.lastname: Zhang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Pei
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics*
chemical_list: C544547:MIRN1 microRNA, human; D035683:MicroRNAs