title: miR-146a suppresses the sensitivity to interferon-α in hepatocellular carcinoma cells.
abstract: BACKGROUND
  Interferon-based (IFN-based) therapy is effective in the treatment of advanced hepatocellular carcinoma (HCC). However, the issue of resistance to this therapy remains to be solved. The aim of this study was to identify microRNAs (miRNAs) that govern the sensitivity to IFN-α in HCC cells.
  
  
  METHODS
  miRNA microarray analysis using IFN-α-resistant clones of PLC/PRF/5 (PLC-Rs) and their parental cells (PLC-P) was conducted. Changes in the anti-cancer effects of IFN-α were studied after gain-of-function and loss-of-function of the candidate miRNA.
  
  
  RESULTS
  miR-146a expression was significantly higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity to IFN-α through the suppression of apoptosis. Further experiments showed that miR-146a-related resistance to IFN-α was mediated through SMAD4.
  
  
  CONCLUSIONS
  The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-α through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy.
authors: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors: Akira
authors: A
authors: Tomokuni
authors: Hidetoshi
authors: H
authors: Eguchi
authors: Yoshito
authors: Y
authors: Tomimaru
authors: Hiroshi
authors: H
authors: Wada
authors: Koichi
authors: K
authors: Kawamoto
authors: Shogo
authors: S
authors: Kobayashi
authors: Shigeru
authors: S
authors: Marubashi
authors: Masahiro
authors: M
authors: Tanemura
authors: Hiroaki
authors: H
authors: Nagano
authors: Masaki
authors: M
authors: Mori
authors: Yuichiro
authors: Y
authors: Doki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy*; D035683:MicroRNAs / Q000235:genetics*; D051901:Smad4 Protein / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein