MiRNA-218Inhibits Osteosarcoma Cell Migration And Invasion By Down-regulating Of TIAM1, MMP2and MMP9

The role of deregulated microRNAs in tumorigenesis is still largely unknown. In this study, we focused on the roles of miR-218in osteosarcoma carcinogenesis.The expression of miRNA-218in human osteosarcoma, adjacent normal tissues and Saos-2human osteosarcoma cells was detected firstly. Then the precise role of miRNA-218in osteosarcoma cells was investigated. Upon transfection with a miR-218expression vector, the proliferation of Saos-2human osteosarcoma cells indicated using ATPlite assay was significantly suppressed, migration of Saos-2cells detected by wound healing and invasion determined using transwell were dramatically inhibited by miRNA-218transfection. Potential target genes of miR-218were predicted and T-cell lymphoma invasion and metastasis1(TIAM1) and Matrix metalloproteinase2(MMP2) and9(MMP9) were identified as the potential targets. This was confirmed by western blotting, which showed that miR-218expression inhibited TIAM1, MMP2and MMP9protein expression. Collectively, these data suggest that miR-218act as a tumor suppressor in osteosarcoma by down-regulating TIAM1, MMP2and MMP9expression. Annexin V and PI staining demonstrated that miR-218has no effects on the apoptosis of Saos-2cells, but it increase the apoptotic sensitivity of Saos-2cells after treating with therapeutic drug-doxorubicin. The same results were obtained from the in vivo Saos-2tumor model that miR-218inhibited the Saos-2tumor growth and has a synergistic inhibition function with doxorubicin.