In conclusion, our findings elucidate that PRMT6 is an epigenetic mediator that promotes CDC20 transcription through histone arginine methylation (H3R2me2a) to mediate ubiquitination and degradation of the cell cycle G1/S phase repressor CDKN1B to facilitate GBM tumorigenesis and progression. Here, CDKN1B is linked to glioblastoma.