| RRC ID |
68801
|
| 著者 |
Takaki Y, Saito Y, Takasugi A, Toshimitsu K, Yamada S, Muramatsu T, Kimura M, Sugiyama K, Suzuki H, Arai E, Ojima H, Kanai Y, Saito H.
|
| タイトル |
Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis.
|
| ジャーナル |
Cancer Sci
|
| 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.
|
| 巻・号 |
105(10)
|
| ページ |
1254-60
|
| 公開日 |
2014-10-1
|
| DOI |
10.1111/cas.12498
|
| PMID |
25117675
|
| PMC |
PMC4462359
|
| MeSH |
Animals
Base Sequence
Carcinoma, Hepatocellular / etiology*
Carcinoma, Hepatocellular / genetics
Cell Line, Tumor
DNA Methylation
Gene Silencing*
Hep G2 Cells
Humans
Liver Neoplasms / etiology*
Liver Neoplasms / genetics
Male
Mice, Inbred C57BL
MicroRNAs / genetics*
Molecular Sequence Data
Non-alcoholic Fatty Liver Disease / complications*
Promoter Regions, Genetic
|
| IF |
4.966
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
