MicroRNA-494 represses osteosarcoma development by modulating ASK-1 related apoptosis complexes

BACKGROUND: MicroRNA (miR)-494 had been proven to be involved in tumor pathogenesis, while studies on miR-494 and osteosarcoma (OS) are still limited. In the current study, we aimed to explore the expression pattern and the roles of miR-494 in the development of OS. METHODS: Mouse models and osteoblastic cells were used to investigate the functions of miR-494. A case-control study including 87 OS patients and 100 controls was also conducted to investigate the prognostic value of miR-494. RESULTS: Animal researches and human studies showed that miR-494 expression level in OS tissue (OST) was down-regulated compared to paracancerous tissue (PT), and had a significant positive association with its level in serum (P<0.05). Gain of miR-494 function suppressed OS tumor growth and promoted apoptosis of OS cells, while loss of miR-494 inhibited apoptosis and promoted invasion of osteoblastic cells. MiR-494 expressions in both OST and serum were correlated with the T stage, lymph node metastasis and distant metastasis of OS (P<0.05). Results of survival analysis showed that compared to patients with high miR-494 level, the overall survival rate in 24 months was significantly lower in the low miR-494 group (P<0.05). In vitro study revealed that miR-494 interacted with apoptosis signal regulating kinase 1 (ASK-1)/serine-threonine kinase receptor-associated protein (STRAP)/14-3-3 complex to promote the activation of tumor necrosis factor-α (TNF-α)/ASK-1-mediated apoptosis. CONCLUSIONS: These results revealed that miR-494 functioned as a tumor suppressor and improved the prognosis of OS via modulating apoptosis complexes.