Overexpression of microRNA-495 suppresses the proliferation and invasion and induces the apoptosis of osteosarcoma cells by targeting high-mobility group nucleosome-binding domain 5

Abstract

It has been suggested that microRNAs (miRNAs) act as critical regulators in tumorigenesis. MicroRNA-495 (miR-495) has been suggested as a cancer-associated miRNA in various types of cancers; however, the role of miR-495 in osteosarcoma is unknown. The aim of the present study was to determine whether miR-495 is involved in osteosarcoma, and to investigate the potential molecular mechanism of its involvement. We found that miR-495 was significantly downregulated in osteosarcoma tissues and cell lines, as detected by real-time quantitative polymerase chain reaction (RT-qPCR). Overexpression of miR-495 inhibited osteosarcoma cell proliferation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation and cell cycle assays. Overexpression of miR-495 induced osteosarcoma cell apoptosis. Moreover, miR-495 overexpression also inhibited osteosarcoma cell invasion. Bioinformatics and luciferase reporter assays demonstrated that miR-495 targets the 3'-untranslated region of high-mobility group nucleosome-binding domain 5 (HMGN5), a potential oncogene in various types of cancers. Overexpression of miR-495 inhibited the expression of HMGN5, cyclin B1, Bcl-2 and matrix metalloproteinase 9. In addition, restoration of HMGN5 protein expression abrogated the miR-495-induced effects. Taken together, the present study indicated that miR-495 suppresses the proliferation and invasion and induces the apoptosis of osteosarcoma cells by targeting HMGN5, providing a novel insight into the molecular pathogenesis of osteosarcoma and suggesting a potential molecular target for the development of an miRNA-targeted therapeutic strategy for osteosarcoma.