Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis
Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis
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DOI：
10.1007/s11684-023-1028-4
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发表时间：
2024-03-11
影响因子：
8.1
通讯作者：
Yu，Zhenhai
中科院分区：
文献类型：
--
作者：
Han，Xue;Ren，Chune;Yu，Zhenhai
ALKBH 5是N6-甲基腺苷（m6 A）修饰的主要调节剂，其在许多生物过程中起着至关重要的作用。在这里，我们表明ALKBH 5是乳腺肿瘤生长所必需的。有趣的是，PRMT 6在R283直接甲基化ALKBH 5，随后促进乳腺肿瘤生长。此外，PRMT 6对ALKBH 5的精氨酸甲基化通过m6 A去甲基化增加LDHA RNA稳定性，导致有氧糖酵解增加。此外，在PRMT 6敲除小鼠中证实了PRMT 6介导的ALKBH 5精氨酸甲基化。总的来说，这些发现将PRMT 6-ALKBH 5-LDHA信号传导轴确定为治疗乳腺癌的新靶点。
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.