Silencing of histone methyltransferase NSD3 reduces cell viability in osteosarcoma with induction of apoptosis

Abstract

NSD3 is a histone lysine methyltransferase that methylates histone H3 at lysine 36. NSD3 is located at chromosome 8p11.23, the locus that exhibits strong cancer relevance. Thus, NSD3 is likely involved in multiple human cancers. Nevertheless, its roles in human carcinogenesis remain unknown. In the present study, we demonstrated that silencing of NSD3 in osteosarcoma, the most common primary bone cancer in children and adolescents, results in a marked decrease in the number of viable cancer cells, accompanied by increases in the cell population at the G2/M phase and the number of apoptotic cells. In addition, 549 NSD3-regulated genes were identified and a set of selected candidate genes were validated. Bioinformatic analysis revealed that NSD3 negatively regulates a number of genes that are involved in the process of negative regulation of signal transduction as well as negative regulation of signaling and cell communication. Our results indicate the oncogenic roles of NSD3 in the development and progression of human osteosarcoma, and implicate NSD3 as a potential molecular target for selective therapy for human osteosarcoma.