Primate-Specific microRNA-637 Inhibits Tumorigenesis in Hepatocellular Carcinoma by Disrupting Signal Transducer and Activator of Transcription 3 Signaling
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摘要MiR-637 (microRNA-637) is a primate-specific miRNA belonging to the small noncoding RNA family, which represses gene regulation at the post-transcriptional expression level. Although it was discovered approximately 5 years ago, its biomedical significance and regulatory mechanism remain obscure. Our preliminary data showed that miR-637 was significantly suppressed in four HCC cell lines and, also, in most of the hepatocellular carcinoma (HCC) specimens, thereby suggesting that miR-637 would be a tumor suppressor in HCC. Simultaneously, the enforced overexpression of miR-637 dramatically inhibited cell growth and induced the apoptosis of HCC cells. The transcription factor, signal transducer and activator of transcription 3 (Stat3), is constitutively activated in multiple tumors, and aberrant Stat3 activation is linked to the promotion of growth and desensitization of apoptosis. Our study showed that Stat3 tyrosine 705 phosphorylation and several Stat3-regulated antiapoptotic genes were down-regulated in miR-637 mimics-transfected and Lv-miR637-infected HCC cells. In addition, miR-637 overexpression negatively regulated Stat3 phosphorylation by suppressing autocrine leukemia inhibitory factor (LIF) expression and exogenous LIF-triggered Stat3 activation and rescued cell growth in these cells. A nude mice model also demonstrated the above-described results, which were obtained from the cell model. Furthermore, we found that LIF was highly expressed in a large proportion of HCC specimens, and its expression was inversely associated with miR-637 expression. Conclusion: Our data indicate that miR-637 acted as a tumor suppressor in HCC, and the suppressive effect was mediated, at least in part, by the disruption of Stat3 activation. (HEPATOLOGY 2011; 54: 2137-2148)
著者Zhang JF, He ML, Fu WM, Wang H, Chen LZ, Zhu X, Chen Y, Xie D, Lai P, Chen G, Lu G, Lin MCM, Kung HF
期刊名稱Hepatology
詳細描述To ORKTS: duplicated record
出版年份2011
月份12
日期1
卷號54
期次6
出版社Wiley: 12 months
頁次2137 - 2148
國際標準期刊號0270-9139
電子國際標準期刊號1527-3350
語言英式英語
Web of Science 學科類別Gastroenterology & Hepatology; GASTROENTEROLOGY & HEPATOLOGY

上次更新時間 2020-27-11 於 00:45