PRMT6是一种I型精氨酸甲基转移酶，不对称地双甲基化组蛋白和非组蛋白的精氨酸残基。越来越多的证据表明，PRMT6在人类恶性肿瘤中扮演着肿瘤介质的角色。在这里，我们的目标是揭示PRMT6在促进胶质母细胞瘤（GBM）增殖中的重要作用和潜在机制。对胶质瘤组织中PRMT6表达的研究表明，PRMT6过度表达，并且PRMT6的高表达与胶质瘤/GBM患者的恶化预后呈负相关。沉默PRMT6抑制了GBM细胞的增殖并诱导细胞周期在G0/G1期中停滞，而过表达PRMT6则产生相反的结果。此外，我们发现PRMT6通过促进其降解来削弱CDKN1B的蛋白稳定性。随后的机制研究显示，PRMT6通过激活组蛋白甲基化标记（H3R2me2a）来维持CDC20的转录，并且CDC20与并不稳定CDKN1B。救援实验结果证实，PRMT6通过CDC20促进泛素化降解CDKN1B和细胞增殖。我们还验证了PRMT6抑制剂（EPZ020411）可以减弱GBM细胞的增殖作用。我们的发现说明，PRMT6作为一个表观遗传介质，通过H3R2me2a促进CDC20的转录以调控CDKN1B的降解，从而促进GBM的进展。针对PRMT6-CDC20-CDKN1B轴心可能是治疗GBM的有希望的策略。© 2023. The Author(s).

PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.© 2023. The Author(s).