Abstract: Objective To explore the role of miR-499 targeting TGF-α mRNA protein in regulating the migration and apoptosis of human osteosarcoma cell line Saos2 and its pathogenesis. Methods The expression differences of miR-499 and TGF-α in osteosarcoma tissues were detected by RT-qPCR. Double luciferase reporter gene assay was used to detect the targeting relationship between miR-499 and TGF-α. Transwell cell assay and TUNEL apoptosis assay were used to detect the migration and apoptosis of Saos2 cells. A nude mouse xenograft model of osteosarcoma was constructed to detect the regulatory mechanism of miR-499/TGF-α axis in vivo. Results In osteosarcoma, miR-499 expression was decreased (P＜0.01) but TGF-α mRNA expression was increased(P＜0.01). miR-499 negatively regulated TGF-α mRNA protein expression (P＜0.01). Transfection of miR-499 simulacrum inhibited the migration and promoted apoptosis of Saos2 cells (P＜0.01), while TGF-α promoted the migration and inhibited apoptosis of Saos2 cells (P＜0.01). miR-499 inhibited the carcinogenic effect of TGF-α. Conclusions miR-499 inhibits the biological function of osteosarcoma cell line Saos2 by inhibiting at TGF-α mRNA protein level which suggests that miR-499 may inhibit the development of osteosarcoma.

Key words: osteosarcoma, miR-499, TGF-α, Saos2