ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly met...ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor growth.Furthermore,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic glycolysis.Moreover,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice.Collectively,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.展开更多
基金supported by research grants from National Natural Science Foundation of China(Nos.81972489 and 82003201)National Natural Science Foundation of Shandong Province(Nos.ZR2020YQ58 and ZR2020QH255)+1 种基金Shandong Province College Science and Technology Plan Project(No.J17KA254)Projects of medical and health technology development program in Shandong Province(No.2018WS057).
文摘ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor growth.Furthermore,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic glycolysis.Moreover,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice.Collectively,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.
