Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met
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Chengcao Sun1,3,*, Ming Sang2,*, Shujun Li1,4, Xiaodong Sun2, Cuili Yang1, Yongyong Xi1, Liang Wang1, Feng Zhang1, Yongyi Bi1, Yunfeng Fu5, Dejia Li1
1Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China
2Central Laboratory of the Fourth Affiliated Hospital in Xiangyang, College of Basic Medical Sciences, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, 442000 Shiyan, P. R. China
3Institute of Global Health, Wuhan University, 430071 Wuhan, P. R. China
4Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P. R. China
5The Third Xiang-ya Hospital of Central South University, 410013 Changsha, P. R. China
*These authors have contributed equally to this work
Yunfeng Fu, e-mail: [email protected]
Dejia Li, e-mail: [email protected]
Keywords: Hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis
Received: May 01, 2015 Accepted: October 07, 2015 Published: October 14, 2015
Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.
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