MicroRNA-494 inhibits proliferation and metastasis of osteosarcoma through repressing insulin receptor substrate-1.

ABSTRACT

Despite microRNA-494 (miR-494) has a well-established role in many types of cancer; the biological function and potential mechanism of miR-494 in human osteosarcoma (OS) has not been elucidated. The aim of this study was therefore to investigate the role and underlying mechanism of miR-494 expression in osteosarcoma. Here, we found that miR-494 was significantly decreased in OS tissues and cell lines compared to the adjacent noncancerous bone tissues (P<0.01) and human normal osteoblast cells (NHOst) (P<0.05), respectively. Functional assays demonstrated that ectopic overexpression of miR-494 could significantly inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth in nude mice model. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a target gene of miR-494 in OS cells. IRS1 expression was upregulated, and inversely correlated with miR-494 expression in clinical OS tissues (r=-0.589, P=0.001). Moreover, downregulation of IRS1 had similar the inhibition effect on cell proliferation, colony formation, migration and invasion of miR-494 overexpression. Overexpresion of miR-494 obviously decreased AKT signal pathway activation. These findings suggested that miR-494 functioned as a tumor suppressor in OS, at least in part, by targeting IRS1.