Inhibition of osteosarcoma cell progression by MacroH2A via the downregulation of cyclin D and cyclin-dependent kinase genes

Abstract

MacroH2A is a histone modification factor the activity of which has been acutely studied in cancer progression, and a number of studies have shown that the progression of certain types of cancer is under regulation by MacroH2A. However, information regarding the underlying molecular mechanisms of MacroH2A inhibition on the cell cycle remains elusive, and elucidating this process may aid in the production of novel treatment strategies. The aim of the current study was to investigate the inhibitory effects of MacroH2A on osteosarcoma cell progression, and the possible molecular mechanisms of this process. MacroH2A overexpression and interference vectors were designed and transfected into U2-OS osteosarcoma cells. The cells underwent reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence assays. The apoptosis rate and cell cycle stage were assayed using flow cytometry. The results revealed that the overexpression of MacroH2A inhibited the progression of U2-OS osteosarcoma cells, and the cells were arrested at the G2/M stage of the cell cycle. The molecular mechanism by which MacroH2A suppresses the cell progression involves the inhibition of the expression of cyclin D and cyclin-dependent kinase (CDK) genes, including cyclin D1, cyclin D2, CDK4, CDK6 and CDK8. Taken together, the present results revealed that MacroH2A is an important modifier of chromatin that downregulates the progression of osteosarcoma cells and triggers disturbance of the cell cycle via the downregulation of cyclin D and CDK genes.