miR-503 is down-regulated in osteosarcoma and suppressed MG63 proliferation and invasion by targeting VEGFA/Rictor.

Abstract

We analyzed the expression of miR-503 in osteosarcoma tissues (OS) and discussed the clinical significance of our findings. To provide a theoretical basis for clinical applications, prognosis prediction and treatment of osteosarcoma, we studied the biological function of miR-503 and its mechanism in MG63 osteosarcoma cells. Real-time polymerase chain reaction (PCR) was used to detect the expression of miR-503 in 45 OS tissues and 20 osteochondroma tumors, analyzing the relationship between clinical pathology and follow-up data. Cox multivariate analysis revealed the clinical and pathological features of the osteosarcoma index and the influence of miR-503 expression on OS prognosis. To observe the effect on cell proliferation and invasion, MG-63 cells were transfected with miR-503. The TargetScan and PicTar bioinformatics method was used to analyze the probable target gene of miR-503 and, combined with the function of the target genes, resulted in a final validation of related pathways. miR-503 was significantly down-regulated in primary OS samples (26/45, 57.8%). The median miR-503 expression level in osteosarcoma was two-fold lower than that in osteochondroma (median expression 6.4 and 13.09, respectively, P< 0.05). The less-expressed miR-503 was associated with Enneking stage (p= 0.004) and invasion (p= 0.015) of OC. Patients with low miR-503 expression had poorer overall survival time. In the multivariate analysis, miR-503 was a significant prognostic factor (P= 0.010). miR-503 can inhibit proliferation and invasion in the MG63 cell line. Using bioinformatics, VEGFA and Rictor were determined to be the likely downstream target genes of miR-503. VEGFA, Rictor, Akt and Erk1/2 were negatively regulated by the overexpression of miR-503. In conclusion, miR-503 has significant tumor-suppressor biological activity and is thus likely to become a new target for the treatment of osteosarcoma.