Down-regulation of c-Met and Bcl2 by microRNA-206, activates apoptosis, and inhibits tumor cell proliferation, migration and colony formation.
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.
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.|Institute of Global Health, Wuhan University, Wuhan 430071, P. R. China.
Chengcao
C
Sun
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
Zhidong
Z
Liu
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.|Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, Wuhan 430071, P. R. China.
Shujun
S
Li
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Cuili
C
Yang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Ruilin
R
Xue
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Yongyong
Y
Xi
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Liang
L
Wang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Suqing
S
Wang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Qiqiang
Q
He
Department of Thoracic Surgery, People's Hospital of Wuhan University, Wuhan 430000, P. R. China.
Jie
J
Huang
Department of Thoracic Surgery, People's Hospital of Wuhan University, Wuhan 430000, P. R. China.
Songping
S
Xie
Department of Thoracic Surgery, People's Hospital of Wuhan University, Wuhan 430000, P. R. China.
Wenyang
W
Jiang
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, P. R. China.
Dejia
D
Li
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D020413:3' Untranslated Regions; C000595707:BCL2 protein, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Bcl2; c-Met; hsa-miRNA-206(miR-206); non-small cell lung cancer (NSCLS); proliferation