MiR-374a promotes the proliferation of human osteosarcoma by downregulating FOXO1 expression.

ABSTRACT

MiRNAs play crucial roles in development of cancer. However, the underlying mechanisms of miRNAs in osteosarcoma (OS) are poorly understood. In the present study, we reported that the expression of miR-374a was markedly upregulated in OS tissues and OS cells compared with the matched adjacent normal tissues and human osteoclast h-FOB cell lines. Overexpression of miR-374a promoted the proliferation and anchorage-independent growth of OS cells, whereas inhibition of miR-374a showed opposite effect. Furthermore, we identified that FOXO1 is the functional target of miR-374a. MiR-374a-induced proliferation was correlated with FOXO1, upregulating of the cell cycle regulator cyclin D1 and downregulating of cyclin-dependent kinase inhibitors p27. In functional assays, FOXO1 downregulation is required for miR-374a-induced OS cell proliferation. In sum, our data provide compelling evidence that a novel mechanism of FOXO1 suppression mediated by miR-374a in OS.