Tumor-suppressive miR-99a inhibits cell proliferation via targeting of TNFAIP8 in osteosarcoma cells.

Osteosarcoma (OS) has been described as the most common primary malignant bone tumor in adolescents and young adults worldwide. MicroRNAs (miRNAs) have demonstrated playing critical role on the cellular biology and development of cancer. However, the essential mechanisms of miRNAs underlying osteosarcoma oncogenesis and progression have not fully understood. In this study, we found that the expression of miR-99a was repressed in OS tissues and cells using qRT-PCR assays. We demonstrated that overexpression of miR-99a inhibits OS cell viability and growth with MTT, colony formation and in vivo mice experiment. In addition, FACS and Annexin V assays identified that miR-99a can induce OS cell cycle progression and cell apoptosis. Furthermore, we demonstrated that TNFAIP8 is a direct target of miR-99a and is upregulated in OS samples and cells. Knockdown of TNFAIP8 significantly attenuated OS cell viability and growth through inhibiting cell cycle and inducing cell apoptosis in vitro and in vivo. These findings establish that miR-99a plays a significant tumor-suppressing role in OS and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.