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

• Published in: Oncotarget 2015-09, Vol.6 (28), p.25533-25574
• Main Authors: Sun, Chengcao, Liu, Zhidong, Li, Shujun, Yang, Cuili, Xue, Ruilin, Xi, Yongyong, Wang, Liang, Wang, Suqing, He, Qiqiang, Huang, Jie, Xie, Songping, Jiang, Wenyang, Li, Dejia
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; Apoptosis; Binding Sites; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Invasiveness; Protein Binding; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Research Paper; RNA Interference; Signal Transduction; Time Factors; Transfection
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4575

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 lines. 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'-untranslated region (3'-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.