MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4.

Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.