Molecular mechanism underlying the suppression of CPB2 expression caused by persistent hepatitis C virus RNA replication

Hiroe Sejima, Shinya Satoh, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Masanori Ikeda, Nobuyuki Kato

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The mechanisms of hepatitis C virus (HCV)-associated hepatocarcinogenesis and disease progression are unclear. We previously observed that the expression level of carboxypeptidase B2 (CPB2) gene was remarkably suppressed by persistent HCV RNA replication in human hepatoma cell line Li23- derived cells. The results of the present study demonstrated that the CPB2 expression in patients with chronic hepatitis C was inversely correlated with several risk factors of hepatic fibrosis or steatosis, although ectopic CPB2 expression did not suppress the expression of fibrogenic or lipogenic genes. The suppressed CPB2 expression was restored by treatment with 5-azacytidine. To clarify the mechanism underlying this phenomenon, we analyzed the CPB2 promoter, and the results revealed that (1) hepatocyte nuclear factor 1 (HNF1), especially HNF1α, was essential for the CPB2 promoter, and (2) CPB2 promoter was not methylated by persistent HCV RNA replication. The expression levels of HNF1α and HNF1β were also not changed by persistent HCV RNA replication. These results suggest the existence of 5-azacytidine-inducible or -reducible unknown factor(s) that can control the CPB2 expression. To evaluate this idea we performed a microarray analysis, and several gene candidates corresponding to the suggested factor(s) were identified.

Original languageEnglish
Pages (from-to)75-88
Number of pages14
JournalActa Medica Okayama
Volume70
Issue number2
Publication statusPublished - 2016

Keywords

  • Carboxypeptidase B2
  • DNA methylation
  • Hepatocyte nuclear factor 1
  • Persistent hepatitis C virus replication
  • Suppression mechanism of CPB2 expression

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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