PRMT5 and neoplasm: In this study we show that i) PRMT5 inhibition sensitizes the GBMNS to TMZ, ii) Inhibition of PRMT5 abrogates the TMZ-induced G2/M cell cycle arrest, iii) LLY-283 treatment downregulates the DNA-DSB repair pathway, particularly HR, iv) Inhibition of PRMT5 increases TMZ-induced DNA damage by blocking the DNA damage repair pathways, v) In vivo, the combination of LLY-283 and TMZ has more enhances the antitumor efficacy and prolongs the survival of tumor-bearing mice.