TY - JOUR
T1 - Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis
AU - Takaki, Yoko
AU - Saito, Yoshimasa
AU - Takasugi, Azusa
AU - Toshimitsu, Kohta
AU - Yamada, Shoji
AU - Muramatsu, Toshihide
AU - Kimura, Masaki
AU - Sugiyama, Kazuo
AU - Suzuki, Hiromu
AU - Arai, Eri
AU - Ojima, Hidenori
AU - Kanai, Yae
AU - Saito, Hidetsugu
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
KW - Fatty liver
KW - Hepatocellular carcinoma
KW - MicroRNA
KW - Non-alcoholic steatohepatitis
KW - miR-122
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U2 - 10.1111/cas.12498
DO - 10.1111/cas.12498
M3 - Article
C2 - 25117675
AN - SCOPUS:84911031215
SN - 1347-9032
VL - 105
SP - 1254
EP - 1260
JO - Cancer science
JF - Cancer science
IS - 10
ER -
