Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, P.R. China.
Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou, Jiangsu 213001, P.R. China.
Oncol Rep. 2017 Nov;38(5):2796-2802. doi: 10.3892/or.2017.5936. Epub 2017 Sep 4.
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.
NSD3 是一种组蛋白赖氨酸甲基转移酶，可将组蛋白 H3 赖氨酸 36 甲基化。NSD3 位于染色体 8p11.23，该基因座与癌症密切相关。因此，NSD3 可能参与多种人类癌症。然而，其在人类癌症发生中的作用尚不清楚。在本研究中，我们证明了沉默骨肉瘤（儿童和青少年中最常见的原发性骨癌）中的 NSD3 会导致存活癌细胞数量明显减少，同时 G2/M 期细胞群体增加和凋亡细胞数量增加。此外，鉴定了 549 个 NSD3 调控的基因，并验证了一组选定的候选基因。生物信息学分析表明，NSD3 负调控涉及负调控信号转导过程以及负调控信号和细胞通讯的许多基因。我们的研究结果表明，NSD3 在人类骨肉瘤的发生和发展中具有致癌作用，提示 NSD3 可能成为人类骨肉瘤选择性治疗的潜在分子靶点。
