miRNA-218 targets multiple oncogenes and is a therapeutic target for osteosarcoma

Survivin is overexpressed in various cancers and is correlated with treatment resistance and prognosis. MicroRNAs (miRNAs) directly regulate several target genes and are potential therapeutic agents for various cancers. The present study evaluated multiple gene targets of miR-218, including survivin, in osteosarcoma and compared the anti-tumor effects of miR-218 with those of YM155, an anti-survivin agent. It assessed the expression levels of miR-218 and survivin in osteosarcoma and osteoblast cell lines, as well as the proliferative, migratory and invasive capacities of cells following treatment with miR-218 or YM155. The form of cell death was assessed using fluorescence-activated cell sorting analysis to examine the expression of invasion ability-related genes. Osteosarcoma cell lines were subcutaneously injected into immunodeficient mice; the mice were then treated with miR-218 or YM155 to assess the anti-tumor effects of these agents. The results showed that miR-218 was downregulated, whereas survivin was overexpressed in the osteosarcoma cell line compared with normal osteoblast cells. The expression of survivin was suppressed upon overexpression of miR-218 (miR-218 group) or administration of YM155 (YM155 group), leading to apoptosis and inhibition of osteosarcoma cell proliferation. Invasion and migration abilities were inhibited in the miR-218 group, but not in the YM155 group. In the animal model, both the miR-218 and YM155 groups showed a reduced tumor volume and decreased survivin expression. In osteosarcoma, miR-218 showed a wider range of therapeutic efficacy compared with YM155, suggesting that miR-218 should be evaluated as a treatment target.