Nrf2驱动表观遗传重编程,并作为诱导转化中KLF4表达和活性的主调节者
Ziwei Wang1, Zhuoyue Bi1, Jessica Bamrah1
1Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY, 11794, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 4, 2025
概括
核因子红色素2相关因子2 (Nrf2) 放大KLF4的表达,促进癌症干细胞. 针对Nrf2和KLF4提供了一种潜在的治疗策略,用于诱导的癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 环境健康 环境健康
背景情况:
- Nrf2激活与癌症的发展有关,特别是在引起的癌症中.
- 暴露于会通过Nrf2-驱动的代谢重编程促进癌症干细胞的形成.
研究的目的:
- 研究KLF4作为处理细胞中Nrf2的转录标的作用.
- 在致癌的背景下阐明Nrf2和KLF4之间的调控关系.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 以确定KLF4位点上的Nrf2结合位点.
- 在Nrf2淘汰赛后对KLF4表达和基因组占用率的分析.
- 在暴露后对致癌基因结合KLF4的评估.
主要成果:
- KLF4是处理的支气管上皮细胞 (BEAS-2B) 中 Nrf2 的直接转录标.
- Nrf2调节KLF4表达和KLF4位置的增强剂活性.
- 暴露会增加KLF4对参与瘤途径的基因的结合,包括STAT3和SOX2.
- 在Nrf2和KLF4之间有一个积极的反循环,放大了它们的致癌功能.
- Nrf2-KLF4的共同占用对于建立活性增强剂至关重要.
结论:
- Nrf2通过放大KLF4的表达和功能,在一定程度上有助于瘤发生.
- Nrf2-KLF4轴在维持癌症干细胞状细胞特性方面发挥着至关重要的作用.
- 同时准Nrf2和KLF4可能是对抗诱导癌症的可行的治疗策略.
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