MiR-146a suppresses the sensitivity to interferon-α in hepatocellular carcinoma cells

Akira Tomokuni, Hidetoshi Eguchi, Yoshito Tomimaru, Hiroshi Wada, Koichi Kawamoto, Shogo Kobayashi, Shigeru Marubashi, Masahiro Tanemura, Hiroaki Nagano, Masaki Mori, Yuichiro Doki

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)675-680
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume414
Issue number4
DOIs
Publication statusPublished - Nov 4 2011

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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