Wuxi Xishan People's Hospital.
Department of Otolaryngology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China.
J Environ Pathol Toxicol Oncol. 2025;44(1):57-71. doi: 10.1615/JEnvironPatholToxicolOncol.2024053754.
Nasopharyngeal carcinoma (NPC) is one of the common malignant tumors in clinic. In the current study, we aim to investigate the effects of PRMT4 on erastin-induced ferroptosis in NPC by cisplatin resistant. PRMT4 expression in patients with NPC by cisplatin was upregulated. PRMT4 upregulation promoted cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. PRMT4 downregulation reduced cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. PRMT4 promoted tumor volume in mice model of erastin-induced NPC by cisplatin. PRMT4 upregulation reduced erastin-induced ferroptosis in NPC cisplatin-resistant cells by mitochondrial damage. PRMT4 upregulation induced Nrf2 protein expression in model of erastin-induced NPC by cisplatin. Nrf2 reduced the effects of si-PRMT4 on cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. Nrf2 inhibitor reduced the effects of PRMT4 on cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. Nrf2 reduced the effects of si-PRMT4 on erastin-induced ferroptosis in NPC cisplatin-resistant cells by mitochondrial damage. PRMT4 protein interlinked with Nrf2 protein to decrease Nrf2 ubiquitination. Methylation increased PRMT4 DNA stability. Collectively, our data reveal that PRMT4 reduced erastin-induced ferroptosis in NPC cisplatin-resistant cells by Nrf2/GPX4 pathway, suggesting that targeting PRMT4 may present as a potential strategy against the development of NPC.
鼻咽癌（NPC）是临床上常见的恶性肿瘤之一。在本研究中，我们旨在探讨 PRMT4 对顺铂耐药 NPC 中依维莫司诱导的铁死亡的影响。PRMT4 在 NPC 患者中的表达被顺铂上调。PRMT4 上调促进了顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡细胞生长。PRMT4 下调减少了顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡细胞生长。PRMT4 促进了顺铂诱导 NPC 小鼠模型中的肿瘤体积。PRMT4 上调通过线粒体损伤减少了顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡。PRMT4 上调诱导了顺铂诱导 NPC 模型中的 Nrf2 蛋白表达。Nrf2 减少了 si-PRMT4 对顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡细胞生长的影响。Nrf2 抑制剂减少了 PRMT4 对顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡细胞生长的影响。Nrf2 通过线粒体损伤减少了 si-PRMT4 对顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡。PRMT4 蛋白与 Nrf2 蛋白相互作用，减少 Nrf2 的泛素化。甲基化增加了 PRMT4 的 DNA 稳定性。综上所述，我们的数据表明，PRMT4 通过 Nrf2/GPX4 通路减少顺铂耐药 NPC 细胞中依维莫司诱导的铁死亡，表明靶向 PRMT4 可能是一种潜在的治疗 NPC 的策略。
