异常的表观遗传修饰参与肿瘤细胞中 Warburg 效应的调节。蛋白质精氨酸甲基转移酶 (PRMT) 介导精氨酸甲基化，在细胞反应中具有关键功能。 PRMT 在多种癌症中不受管制，但它们在癌症中 Warburg 效应中的确切作用尚不清楚。本研究的实验表明，PRMT1 在葡萄糖充足的条件下高表达。 PRMT1 通过上调 PTBP1 诱导 PKM2/PKM1 比率增加，进而促进非小细胞肺癌 (NSCLC) 中的有氧糖酵解。 p53缺陷和p53突变的NSCLC中PRMT1水平保持相对不变，而p53野生型NSCLC中的表达在葡萄糖不足的条件下降低。值得注意的是，葡萄糖缺乏条件下 p53 的激活可以抑制 USP7 并进一步加速 PRMT1 的多泛素依赖性降解。褪黑激素是一种抑制葡萄糖摄入的激素，可显着抑制 p53 野生型 NSCLC 的细胞增殖，而褪黑激素和 USP7 抑制剂 P5091 的组合增强了 p53 缺陷型 NSCLC 的抗癌活性。我们的集体研究结果支持 PRMT1 在调节 NSCLC 中 Warburg 效应中的作用。此外，褪黑激素和 USP7 抑制剂的联合治疗显示出良好的疗效，为开发基于 PRMT1 的疗法以改善 p53 缺陷的 NSCLC 结局提供了理论依据。© 2024。作者。

Abnormal epigenetic modifications are involved in the regulation of Warburg effect in tumor cells. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have critical functions in cellular responses. PRMTs are deregulated in a variety of cancers, but their precise roles in Warburg effect in cancer is largely unknown. Experiments from the current study showed that PRMT1 was highly expressed under conditions of glucose sufficiency. PRMT1 induced an increase in the PKM2/PKM1 ratio through upregulation of PTBP1, in turn, promoting aerobic glycolysis in non-small cell lung cancer (NSCLC). The PRMT1 level in p53-deficient and p53-mutated NSCLC remained relatively unchanged while the expression was reduced in p53 wild-type NSCLC under conditions of glucose insufficiency. Notably, p53 activation under glucose-deficient conditions could suppress USP7 and further accelerate the polyubiquitin-dependent degradation of PRMT1. Melatonin, a hormone that inhibits glucose intake, markedly suppressed cell proliferation of p53 wild-type NSCLC, while a combination of melatonin and the USP7 inhibitor P5091 enhanced the anticancer activity in p53-deficient NSCLC. Our collective findings support a role of PRMT1 in the regulation of Warburg effect in NSCLC. Moreover, combination treatment with melatonin and the USP7 inhibitor showed good efficacy, providing a rationale for the development of PRMT1-based therapy to improve p53-deficient NSCLC outcomes.© 2024. The Author(s).