RNF216通过促进p53泛素化抑制肺腺癌铁下垂。

IF 3.2
Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-06-12 DOI:10.1177/09603271251336793
Jiasheng Wu, Weiqiang Mo, Haiqin Wang, Jianping Jiang, Jing Zhao
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引用次数: 0

摘要

肺腺癌(LUAD)是非小细胞肺癌中最常见的亚型,也是全球癌症相关死亡的主要原因。本研究探讨了无名指蛋白216 (RNF216)在LUAD进展中的作用。方法检测srnf216在LUAD组织和细胞中的表达。功能试验评估细胞活力、迁移、侵袭和铁下垂。机制研究确定了RNF216在调节p53泛素化和稳定性中的作用。在体内,异种移植模型评估肿瘤生长和铁下垂。结果rnf216在LUAD组织和细胞系中明显过表达。功能研究表明,沉默RNF216抑制LUAD细胞的增殖、迁移和侵袭,同时诱导铁凋亡,其特征是活性氧(ROS)、脂质过氧化(LPO)和细胞内Fe2+积累增加。机制上,RNF216敲低通过降低p53的泛素化来稳定p53,从而促进铁下垂。这些发现在体内得到了证实,在异种移植模型中,RNF216沉默显著抑制肿瘤生长并增强铁下垂。结论RNF216是一个关键的致癌驱动因子,通过p53泛素化抑制铁凋亡,从而加速LUAD的进展。靶向RNF216可能是一种很有前途的治疗策略,可以诱导铁下垂和对抗LUAD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RNF216 inhibits ferroptosis in lung adenocarcinoma by promoting p53 ubiquitination.

PurposeLung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer and a leading cause of cancer-related mortality worldwide. This study investigates the role of Ring Finger Protein 216 (RNF216) in LUAD progression.MethodsRNF216 expression was evaluated in LUAD tissues and cells. Functional assays evaluated cell viability, migration, invasion, and ferroptosis in vitro. Mechanistic investigations defined RNF216's role in regulating p53 ubiquitination and stability. In vivo, xenograft models evaluated tumor growth and ferroptosis.ResultsRNF216 was markedly overexpressed in LUAD tissues and cell lines. Functional studies demonstrated that silencing RNF216 suppressed LUAD cell proliferation, migration, and invasion while inducing ferroptosis, characterized by increased reactive oxygen species (ROS), lipid peroxidation (LPO), and intracellular Fe2+ accumulation. Mechanistically, RNF216 knockdown stabilized p53 by reducing its ubiquitination, thereby promoting ferroptosis. These findings were corroborated in vivo, where RNF216 silencing significantly inhibited tumor growth and enhanced ferroptosis in xenograft models.ConclusionsOur results establish RNF216 as a pivotal oncogenic driver that accelerates LUAD progression by suppressing ferroptosis through p53 ubiquitination. Targeting RNF216 may represent a promising therapeutic strategy to induce ferroptosis and combat LUAD.

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