VEGF-mediated suppression of cell proliferation and invasion by miR-410 in osteosarcoma.
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. The aberrant expression of miRNA has become a major focus in cancer research. This study aimed to investigate the importance of miR-410 in the diagnosis and therapy of osteosarcoma (OS). Western blot analysis showed that the expression of VEGF was higher in Saos-2 and MG-63 cells than that in three other OS cell lines. We also found that miR-410 was lowly expressed and inversely correlated with VEGF expression in OS specimens. Over-expression of miR-410 had a greater repression on VEGF expression than other candidate VEGF-targeting miRNAs. Luciferase reporter assay demonstrated that miR-410 directly decreased VEGF expression by targeting its 3'-untranslated region. Further investigation demonstrated the regulation of miR-410 in OS cells via VEGF. In vitro MTT assay, Transwell, and flow cytometry showed that transfection of the miR-410 expression plasmid inhibited cell proliferation and contributed to apoptosis in OS cells. Moreover, restoration of VEGF reversed the effect of miR-410 on OS cells, and upregulated the expression of phosphorylated AKT. Finally, overexpression of miR-410 also showed a negative effect on tumor growth in vivo. Our findings suggest a cooperative relationship between miR-410 and VEGF in OS cell regulation. This information may help researchers to better understand miRNA regulation in cancer and provide a rationale for developing miRNA-based strategies for OS treatment.
Department of Orthopedics, Affiliated Hospital, Logistics University of Chinese People's Armed Police Forces, No. 220 Chenglin Road, Hedong district, Tianjin, 300162, China, zhaodongtj@163.com.
Dong
D
Zhao
Peng
P
Jia
Wenliang
W
Wang
Guangling
G
Zhang
D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
C568527:MIRN410 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A