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

• Published in: Oncotarget 2015-11, Vol.6 (37), p.39756-39792
• Main Authors: Sun, Chengcao, Sang, Ming, Li, Shujun, Sun, Xiaodong, Yang, Cuili, Xi, Yongyong, Wang, Liang, Zhang, Feng, Bi, Yongyi, Fu, Yunfeng, Li, Dejia
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Blotting, Western; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - genetics; Cyclin D1 - genetics; Cyclin D1 - metabolism; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Microscopy, Fluorescence; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Research Paper; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Survival Analysis; Tumor Burden - genetics; Xenograft Model Antitumor Assays - methods
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.5476

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.