title: MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-α.
abstract: OBJECTIVE
  Increasing evidence suggests that miRNAs have a profound impact on host defense to Hepatitis C virus (HCV) infection and clinical outcome of standard HCV therapy. In this study, we investigated modulation of miRNA expression in Huh7.5 hepatoma cells by HCV infection and in vitro interferon-αtreatment.
  
  
  METHODS
  MiRNA expression profiling was determined using Human miRNA TaqMan® Arrays followed by rigorous pairwise statistical analysis. MiRNA inhibitors assessed the functional effects of miRNAs on HCV replication. Computational analysis predicted anti-correlated mRNA targets and their involvement in host cellular pathways. Quantitative RTPCR confirmed the expression of predicted miRNA-mRNA correlated pairs in HCV-infected Huh7.5 cells with and without interferon-α.
  
  
  RESULTS
  Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-α treatment (p<0.01). The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection.
  
  
  CONCLUSIONS
  HCV differentially modulates miRNAs to facilitate entry and early establishment of infection in vitro. Interferon-α appears to neutralize the effect of HCV replication on miRNA regulation thus providing a potential mechanism of action in eradicating HCV from hepatocytes.
authors: Immunopathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Xiaozhen
authors: X
authors: Zhang
authors: Marybeth
authors: M
authors: Daucher
authors: David
authors: D
authors: Armistead
authors: Rodney
authors: R
authors: Russell
authors: Shyam
authors: S
authors: Kottilil
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha