Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis.
Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis.
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DOI：
10.1111/cas.12498
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发表时间：
2014-10
期刊：
影响因子：
5.7
通讯作者：
Saito H
中科院分区：
文献类型：
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作者：
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
非酒精性脂肪性肝炎（NASH）已成为肥胖、糖尿病和代谢综合征患者慢性肝病和非病毒依赖性肝细胞癌（HCC）的常见原因。为了揭示NASH肝癌发生的分子机制，分析了STAM小鼠（NASH-HCC动物模型）中微小RNA（miRNA）的表达谱。还在42个HCC组织的临床样品中检测了MicroRNA表达。6、8、12和18周龄的STAM小鼠的肝脏组织学图像分别显示与脂肪肝、NASH、肝硬化（LC）和HCC相容的发现。miR-122在18周龄非肿瘤LC中的表达显著低于12周龄LC。在18周龄时，相对于非肿瘤LC，HCC中miR-122的表达进一步降低。在显示大泡性脂肪变性和HCC的肝组织的临床样品中，miR-122的表达也降低，这与NASH模型小鼠中的发现一致。DNA甲基化分析显示，miR-122的沉默不是由启动子区域的DNA超甲基化介导的。这些结果表明，miR-122的沉默是NASH肝癌发生过程中的早期事件，miR-122可能是评估NASH患者HCC风险的新分子标志物。
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.
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影响因子：
8
作者：
Saito, Y.;Suzuki, H.;Hibi, T.
通讯作者：
Hibi, T.
影响因子：
25.7
作者：
Li, Zhen-Ya;Xi, Yang;Liang, Chih-Chuan
通讯作者：
Liang, Chih-Chuan
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
影响因子：
11.2
作者：
Gramantieri, Laura;Ferracin, Manuela;Negrini, Massimo
通讯作者：
Negrini, Massimo
DOI：
10.1038/nrm3313
发表时间：
2012-03-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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