miR-494 inhibits cell proliferation and metastasis via targeting of CDK6 in osteosarcoma

Abstract

Tumorigenesis is a multistep process involving various cell growth-associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in onco-genesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)-494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR-494 exerts tumor-suppressive effects in the development of OS, the effects of miR-494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR-494 in MG-63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR-494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR-494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR-494, the results of which indicated that miR-494 directly targeted cyclin-dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription-quantitative poly-merase chain reaction and western blot analyses suggested that the elevated expression of miR-494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR-494/CDK6 axis has a significant tumor-suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS.