Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis

Yoko Takaki, Yoshimasa Saito, Azusa Takasugi, Kohta Toshimitsu, Shoji Yamada, Toshihide Muramatsu, Masaki Kimura, Kazuo Sugiyama, Hiromu Suzuki, Eri Arai, Hidenori Ojima, Yae Kanai, Hidetsugu Saito

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42 Citations (Scopus)

Abstract

Non-alcoholic steatohepatitis (NASH) has emerged as a common cause of chronic liver disease and virus-independent hepatocellular carcinoma (HCC) in patients with obesity, diabetes, and metabolic syndrome. To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles were analyzed in STAM mice, a NASH-HCC animal model. MicroRNA expression was also examined in 42 clinical samples of HCC tissue. Histopathological images of the liver of STAM mice at the ages of 6, 8, 12, and 18 weeks showed findings compatible with fatty liver, NASH, liver cirrhosis (LC), and HCC, respectively. Expression of miR-122 in non-tumor LC at the age of 18 weeks was significantly lower than that in LC at the age of 12 weeks. Expression of miR-122 was further decreased in HCCs relative to non-tumor LC at the age of 18 weeks. Expression of miR-122 was also decreased in clinical samples of liver tissue showing macrovesicular steatosis and HCC, being consistent with the findings in the NASH model mice. DNA methylation analysis revealed that silencing of miR-122 was not mediated by DNA hypermethylation of the promoter region. These results suggest that silencing of miR-122 is an early event during hepatocarcinogenesis from NASH, and that miR-122 could be a novel molecular marker for evaluating the risk of HCC in patients with NASH. The results of this study demonstrate that miR-122 is silenced at the early stage of hepatocarcinogenesis from NASH.

Original languageEnglish
Pages (from-to)1254-1260
Number of pages7
JournalCancer science
Volume105
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

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Keywords

  • Fatty liver
  • Hepatocellular carcinoma
  • MicroRNA
  • Non-alcoholic steatohepatitis
  • miR-122

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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