miR-590-3p is a novel microRNA which suppresses osteosarcoma progression by targeting SOX9

Osteosarcoma is the most common primary bone malignancy and arises primarily in the metaphyseal ends of long bones in children and adolescents. m iR-590 has been found to have anti-tumor effects in many other cancers. However, the role of miR-590-3p in osteosarcoma is poorly understood. In this study, we show that miR-590-3p was significantly decreased both in osteosarcoma tissues and cell lines, suggesting a potential role of miR-590-3p in osteosarcoma. Over-expression of miR-590-3p inhibited U2OS cell viability as shown by the CCK-8 assay and clonogenic assay. Ki-67 immunofluorescence staining and cell cycle analysis revealed that up-regulation of miR-590-3p inhibited U2OS cell proliferation. Transfection with miR-590-3p mimics suppressed PCNA, Cyclin D1 and CDK4 expression and increased p53 and p21 expression. In addition, U2OS cells transfected with miR-590-3p mimics exhibited reduced cell invasion and migration, characterized by the wound healing assay and transwell assay. Furthermore, bioinformatics analysis demonstrated that SOX9 was a potential target of miR-590-3p. SOX9 was up-regulated in osteosarcoma tissues. Transfection with miR-590-3p mimics markedly suppressed SOX9 expression both at the mRNA level and protein level. Dual luciferase assay validated the direct binding site of miR-590-3p on SOX9. Exogenous SOX9 expression in U2OS cells at least partially reversed the effects of miR-590-3p in U2OS cells. Enforced SOX9 expression restored cell viability in osteosarcoma cells transfected with miR-590-3p mimics. In addition, over-expression of SOX9 restored decreased cell metastasis properties caused by transfection with miR-590-3p mimics in osteosarcoma cells. In summary, these results indicated that miR-590-3p is an anti-cancer miRNA that can inhibit proliferation and metastasis in osteosarcoma cells. Our findings provide a novel insight into the biological function of miR-590-3p in osteosarcoma and SOX9 may be a potential therapeutic target for osteosarcoma.