Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C

Akihito Tsubota, Kaoru Mogushi, Hideki Aizaki, Ken Miyaguchi, Keisuke Nagatsuma, Hiroshi Matsudaira, Tatsuya Kushida, Tomomi Furihata, Hiroshi Tanaka, Tomokazu Matsuura

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3 Citations (Scopus)

Abstract

Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray data between treatment responses. Quantitative real-time polymerase chain reaction validated the gene signatures from 130 patients who were infected with hepatitis C virus genotype 1b and treated with pegylated interferon-alpha and ribavirin combination therapy. The correlation between mRNA and microRNA was evaluated using in silico analysis and in vitro siRNA and microRNA inhibition/ overexpression experiments. Multivariate regression analysis identified that the independent variables IL28B SNP rs8099917, hsa-miR-122-5p, hsa-miR-17-5p, and MAP3K8 were significantly associated with a poor virologic response. MAP3K8 and miR-17-5p expression were inversely correlated with treatment response. Furthermore, miR-17-5p repressed HCV production by targeting MAP3K8. Collectively, the data suggest that several molecules and the inverse correlation between mRNA and microRNA contributed to a host genetic refractory hepatitis C treatment response.

Original languageEnglish
Article numbere97078
JournalPloS one
Volume9
Issue number5
DOIs
Publication statusPublished - 2014 May 12

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Tsubota, A., Mogushi, K., Aizaki, H., Miyaguchi, K., Nagatsuma, K., Matsudaira, H., Kushida, T., Furihata, T., Tanaka, H., & Matsuura, T. (2014). Involvement of MAP3K8 and miR-17-5p in poor virologic response to interferon-based combination therapy for chronic hepatitis C. PloS one, 9(5), [e97078]. https://doi.org/10.1371/journal.pone.0097078