MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2009-11, Vol.66 (2), p.169-175
• Main Authors: Liu, Bo, Peng, Xiao-Chun, Zheng, Xiao-Li, Wang, Jun, Qin, Yong-Wen
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene therapy; Growth Inhibitors - genetics; Growth Inhibitors - metabolism; Hematology, Oncology and Palliative Medicine; Humans; Lung - metabolism; Lung cancer; Lung Neoplasms - therapy; Medical sciences; Mice; Mice, Inbred BALB C; MicroRNAs - genetics; MicroRNAs - metabolism; miR-126; Pneumology; Pulmonary/Respiratory; Tumors; Tumors of the respiratory system and mediastinum; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2009.01.010

Abstract 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 ± 0.0757 g, 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.