MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo.
Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis, and its expression is up-regulated in many carcinomas. In the present study, we found that a microRNA miR-126 has a binding site in 3'-untranslated region of the VEGF-A mRNA. In eight lung cancer cell lines, expression of miR-126 was down-regulated. Reporter gene assay showed that the co-transfection of mir-126 expression vector with pLuc-VEGF/mir126BS could reduce the activity of luciferase. Transfection experiments showed that miR-126 could decrease the expression of VEGF-A. Three human lung carcinoma cell lines A549, Y-90 and SPC-A1 were investigated as cancer models in vitro, and A549 infected by lentivirus-miR-126 (LV-miR-126) was studied in tumor xenograft model. Infection of LV-miR-126 can down-regulate the expression of VEGF-A in A549, Y-90 and SPC-A1 cell lines and can inhibit the growth of these cells. In addition, flow cytometry analysis revealed that LV-miR-126 infection can induce cell cycle G1 arrest in A549, Y-90 and SPC-A1 cells. Furthermore, in nude mice, the average weight of A549 tumor nodules in experimental group was reduced from 0.8035+/-0.1521 to 0.6235+/-0.0757g, with the inhibitive rate being 22.4%. All these results revealed that miR-126 may have a tumor suppressor function in lung cancer cells and could be a promising treatment in anticancer therapy.
Liu
Bo
B
Cardiovascular Department, ChangHai Hospital, Shanghai, China.
Peng
Xiao-Chun
XC
Zheng
Xiao-Li
XL
Wang
Jun
J
Qin
Yong-Wen
YW
D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D006131:Growth Inhibitors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A