Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis
Version of Record online: 25 SEP 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 10, pages 1254–1260, October 2014
How to Cite
Cancer Sci 105 (2014) 1254–1260
Japan Society for Promotion of Science; Takeda Science Foundation; the Ministry of Education, Culture, Sports, Science and Technology of Japan.
- Issue online: 22 OCT 2014
- Version of Record online: 25 SEP 2014
- Accepted manuscript online: 13 AUG 2014 02:10AM EST
- Manuscript Accepted: 3 AUG 2014
- Manuscript Revised: 31 JUL 2014
- Manuscript Received: 20 JAN 2014
- Japan Society for Promotion of Science. Grant Number: 26290049
- Takeda Science Foundation
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Fatty liver;
- hepatocellular carcinoma;
- miR-122 ;
- non-alcoholic steatohepatitis
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.