MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3

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• 作者：Yanxin Lu ; Xupeng Yue ; Yuanyuan Cui ; Jufeng Zhang ; KeWei Wang
• 关键词：miR-124 ; STAT3 ; Hepatocellular carcinoma ; Proliferation ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：29 November, 2013
• 年：2013
• 卷：441
• 期：4
• 页码：873-879
• 全文大小：1890 K

文摘

The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3鈥?UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC.