Down-regulation of <i>c-Met</i> and <i>Bcl2</i> by microRNA-206, activates apoptosis, and inhibits tumor cell proliferation, migration and colony formation

Abstract

// Chengcao Sun 1, 2, * , Zhidong Liu 3, * , Shujun Li 1, 4, * , Cuili Yang 1 , Ruilin Xue 1 , Yongyong Xi 1 , Liang Wang 1 , Suqing Wang 1 , Qiqiang He 1 , Jie Huang 5 , Songping Xie 5 , Wenyang Jiang 5 , Dejia Li 1 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China 2 Institute of Global Health, Wuhan University, Wuhan 430071, P. R. China 3 Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China 4 Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, Wuhan 430071, P. R. China 5 Department of Thoracic Surgery, People's Hospital of Wuhan University, Wuhan 430000, P. R. China * These authors have contributed equally to this work Correspondence to: Dejia Li, e-mail: lodjlwhu@sina.com Keywords: hsa-miRNA-206(miR-206), c-Met, Bcl2, non-small cell lung cancer (NSCLS), proliferation Received: April 08, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: July 13, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: July 25, 2015 ABSTRACT Hsa-miRNA-206 (miR-206), highly expressed in skeletal muscle, has recently been discovered to have anticancer properties in different tissues. However, the role of miR-206 on lung cancer is still ambiguous. In this study, we investigated the role of miR-206 on the development of lung cancer. The results indicated that miR-206 expression was suppressed in lung cancer tissues and very low levels were found in non-small cell lung cancer (NSCLS) cell liness. Transient transfection of miR-206 into cultured A549 and SK-MES-1 cells led to significant decrease in cell growth, migration, invasion and colony formation, and promoted cell apoptosis. Using bioinformatics, we identified putative miR-206 binding sites within the 3&prime;-untranslated region (3&prime;-UTR) of the human c-Met and Bcl2 mRNA. The expression of c-Met and Bcl2 proteins were shown to be down-regulated after treated with miR-206 by subsequent Western blot and qRT-PCR analysis. Conversely, up-regulation of c-Met and Bcl2 were confirmed in tissue samples of human lung cancer, with its level inversely correlated with miR-206 expression. In addition, miR-206 also decreased the gene expression of MMP-9, CCND1 and CCND2 while increased the gene expression of p57 (Kip2) in A549 and SK-MES-1 cells. Taken together, our results demonstrated that miR-206 suppressed c-Met and Bcl2 expression in NSCLS and could function as a potent tumor suppressor in c-Met/Bcl2-over expressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation, migration, invasion and apoptosis, leading to NSCLS development.