LRRC45通过竞争性KEAP1相互作用稳定NRF2来加速膀癌的发展和铁灭的抑制
Linwei Fan1, Dingfan Guo2, Chao Zhu1
1Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
Free radical biology & medicine
|November 10, 2024
概括
富含白的重复含有蛋白45 (LRRC45) 在膀癌中被上调,通过稳定核因素红色素2相关因子2 (NRF2) 来促进瘤生长. 准LRRC45可能提供新的膀癌疗法.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 中心体调节失调与瘤的发展和进展有关.
- 富含白的重复含有蛋白45 (LRRC45),一个中心体链接蛋白,被确定为膀癌的关键参与者.
- 增加LRRC45表达与膀癌患者预后不佳相关.
研究的目的:
- 研究LRRC45在膀癌进展中的作用.
- 阐明LRRC45影响瘤生长和细胞死亡的分子机制.
- 探索LRRC45作为膀癌的潜在治疗点.
主要方法:
- 对单细胞RNA测序 (scRNA-seq) 数据的分析,以确定膀癌中升调的基因.
- 功能性研究涉及膀癌细胞中LRRC45的耗尽.
- 研究细胞内铁,活性氧物种 (ROS) 和铁灭诱导.
- 确定LRRC45,凯尔奇样ECH相关蛋白1 (KEAP1) 和核因素红色素2相关因子2 (NRF2) 之间的相互作用的机制研究.
主要成果:
- 在膀癌中,LRRC45显著上调,并与预后不佳有关.
- LRRC45的枯竭抑制了膀癌细胞的增殖,并诱导了铁亡.
- LRRC45通过与KEAP1进行竞争性相互作用来促进NRF2的核转移,从而增强NRF2的抗ferroptotic活性.
- 在LRRC45耗尽后观察到细胞内铁和ROS水平的增加.
结论:
- LRRC45通过稳定NRF2并促进瘤发生,在膀癌中发挥关键的瘤原作用.
- 抑制LRRC45会触发铁亡,这是一种依赖铁的细胞死亡途径.
- 准LRRC45为膀癌治疗提供了一个有前途的治疗策略.
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