Yoko Takaki1, Yoshimasa Saito2,1, Azusa Takasugi1, Kohta Toshimitsu1, Shoji Yamada1, Toshiki Muramatsu1, Masaki Kimura1, Kazuo Sugiyama2, Hiromu Suzuki3, Eri Arai4, Hidenori Ojima4, Yae Kanai4, Hidetsugu Saito2,1
1Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan
2Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
3Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan
4Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
Tóm tắt
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.
