Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met

Abstract

// Chengcao Sun 1, 3, * , Ming Sang 2, * , Shujun Li 1, 4 , Xiaodong Sun 2 , Cuili Yang 1 , Yongyong Xi 1 , Liang Wang 1 , Feng Zhang 1 , Yongyi Bi 1 , Yunfeng Fu 5 , Dejia Li 1 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China 2 Central 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 3 Institute of Global Health, Wuhan University, 430071 Wuhan, P. R. China 4 Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P. R. China 5 The Third Xiang-ya Hospital of Central South University, 410013 Changsha, P. R. China * These authors have contributed equally to this work Correspondence to: Yunfeng Fu, e-mail: fuyfeng427@163.com Dejia Li, e-mail: lodjlwhu@sina.com 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 ABSTRACT 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.