MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma
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Wei-xun Chen1,*, Zhan-guo Zhang1,*, Ze-yang Ding1, Hui-fang Liang1, Jia Song1, Xiao-long Tan1, Jing-jing Wu1, Guang-zhen Li1, Zhuo Zeng1, Bi-xiang Zhang1, Xiao-ping Chen1
1Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
*These authors have contributed equally to this work
Bi-xiang Zhang, e-mail: [email protected]
Xiao-ping Chen, e-mail: [email protected]
Keywords: MiR-630, microRNA, HCC, EMT, TGF-β
Received: September 21, 2015 Accepted: February 24, 2016 Published: March 14, 2016
The epithelial-mesenchymal transition (EMT) is the key process that drives tumor metastasis. Accumulating evidence suggests that the deregulation of some microRNAs (miRNAs), is implicated in this process. Here, we highlight the function and molecular mechanism of miR-630 and its potential clinical application in hepatocellular carcinoma (HCC). First, we identified the clinical relevance of miR-630 expression in a screen of 97 HCC patient tissues. Patients with low miR-630 expression had higher recurrence rates and shorter overall survival than those with high miR-630 expression. Functional studies demonstrated the overexpression of miR-630 in HCC cells attenuated the EMT phenotype in vitro. Conversely, inhibition of miR-630 promoted EMT in HCC cells. Mechanistically, our data revealed that miR-630 suppressed EMT by targeting Slug. Knockdown of Slug expression reversed miR-630 inhibitor-mediated EMT progression. Furthermore, we found that the TGF-β-Erk/SP1 and JNK/c-Jun signaling pathways repressed miR-630 transcription through occupying transcription factor binding sites. Ectopic expression of miR-630 restored the TGF-β-activated EMT process. Taken together, these findings demonstrate, in HCC cells, miR-630 exerts its tumor-suppressor functions through the TGF-β-miR-630-Slug axis and provides a potential prognostic predictor for HCC patients.
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