Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met.
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.
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.|Institute of Global Health, Wuhan University, 430071 Wuhan, P. R. China.
Chengcao
C
Sun
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.
Ming
M
Sang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.|Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P. R. China.
Shujun
S
Li
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.
Xiaodong
X
Sun
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Cuili
C
Yang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Yongyong
Y
Xi
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Liang
L
Wang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Feng
F
Zhang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Yongyi
Y
Bi
The Third Xiang-ya Hospital of Central South University, 410013 Changsha, P. R. China.
Yunfeng
Y
Fu
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P. R. China.
Dejia
D
Li
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D019859:Proto-Oncogene Proteins c-met
Hsa-miRNA-139-5p (miR-139-5p); apoptosis; c-Met; non-small cell lung cancer (NSCLC); proliferation