The growing number of findings demonstrate that nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax domain-containing 3 (NSD3) is amplified and overexpressed in multiple cancer types. Nevertheless, the biological roles of NSD3 in carcinogenesis have not been well understood. In this review, we summarize the current knowledge on the mechanisms underlying NSD3 regulation in different cancers. In addition, NSD3 may serve as a potential druggable target for selective cancer therapy in the future.

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.

Objective: To compare the difference in efficacy between open PLIF and UBE for lumbar spinal stenosis and the effect on postoperative adjacent segment instability. Method: The clinical data of 37 patients with PLIF and 32 patients with UBE for lumbar spinal stenosis were retrospectively analyzed to compare the differences in perioperative conditions and short- and medium-term outcomes. Results: All 69 patients completed the surgery successfully. The operating time, number of intraoperative fluoroscopies and hospital days were higher in the UBE group than in the open PLIF group. Intraoperative bleeding and postoperative drainage were lower than in the open PLIF group (P < 0.05). The visual analogue scale (VAS) of low back pain was lower in the UBE group than in the open PLIF group at 1 month and 3 months postoperatively (P < 0.05), and there were no statistically significant VAS scores for low back pain in the two groups at 1 day and 6 months postoperatively (P > 0.05). Leg pain VAS scores were lower in the UBE group than in the open PLIF group at 1 month, 3 months and 6 months postoperatively (P < 0.05), and leg pain VAS scores were not statistically significant in both groups at 1 day postoperatively (P > 0.05). The ODI index was lower in the UBE group than in the open PLIF group at 1 day and 1 month postoperatively (P < 0.05) and was not statistically significant in the two groups at 3 months and 6 months postoperatively (P > 0.05). There was no statistically significant difference between the two groups in postoperative interbody height, sagittal diameter of the spinal canal, efficacy of modified MacNab and interbody fusion (P > 0.05). The open PLIF group was more prone to postoperative adjacent vertebral instability than the UBE group, and the difference was statistically significant (P < 0.05). Conclusion: With appropriate indications, the open PLIF group and the UBE group had similar short- and medium-term clinical outcomes for the treatment of lumbar spinal stenosis, but patients in the UBE group had better symptomatic improvement than the open PLIF group at 3 months postoperatively, and the effect on postoperative adjacent vertebral instability was smaller in the endoscopic group than in the open PLIF group.

Low back pain has become a serious social and economic burden and the leading cause of disability worldwide. Among a variety of pathophysiological triggers, intervertebral disc (IVD) degeneration plays a primary underlying role in causing such pain. Specifically, multiple independent endplate changes have been implicated in the initiation and progression of IVD degeneration. In this study, we built a signaling network comprising both well-characterized IVD pathology-associated proteins as well as some potentially correlated proteins that have been associated with one or more of the currently known pathology-associated proteins. We then screened for the potential IVD degeneration-associated proteins using patients’ normal and degenerative endplate specimens. Short hairpin RNAs for receptor interacting serine/threonine kinase 1 (RIPK1) were constructed to examine the effects of RIPK1 knockdown in primary chondrocyte cells and in animal models of caudal vertebra intervertebral disc degeneration in vivo. RIPK1 was identified as a potential IVD degeneration-associated protein based on IVD pathology-associated signaling networks and the patients’ degenerated endplate specimens. Construction of the short hairpin RNAs was successful, with short-term RIPK1 knockdown triggering inflammation in the primary chondrocytes, while long-term knockdown triggered apoptosis through cleavage of the caspase 3 pathway, down-regulated NF-κB and mitogen-activating protein kinase (MAPK)s cascades, and decreased cell survival and inflammation. Animal models of caudal vertebra intervertebral disc degeneration further demonstrated that apoptosis was induced by up-regulation of tumor necrosis factor (TNF) accompanied by down-regulation of NF-κB and MAPKs cascades that are dependent on caspase and RIPK1. These results provide proof-of-concept for developing novel therapies to combat IVD degeneration through interfering with RIPK1-mediated apoptosis signaling pathways especially in patients with RIPK1 abnormality.

Background: Renal cell carcinoma (RCC) accounts for around 85% of all primary kidney neoplasms, which is one of top 10 common cancers worldwide. Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), belonging to NSD protein family, functions as an oncogene in the pathogenesis of multiple cancers.