慢性IL-1-暴露的LNCaP细胞演化高基数p62-KEAP1复合积累和NRF2/KEAP1-依赖和独立的过敏营养缺乏反应
Haley Dahl-Wilkie1, Jessica Gomez1, Anastasia Kelley1
1Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA.
Cells
|February 12, 2025
概括
长期暴露在前列腺癌细胞中的介质素-1 (IL-1) 会改变它们对营养压力的反应. 这导致p62/KEAP1轴在调节基因表达中的新型NRF2独立作用.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子信号传递是分子信号传递.
背景情况:
- 慢性炎症是癌症的标志,其中互白素-1 (IL-1) 促进前列腺癌 (PCa) 的进展.
- 支架蛋白p62在细胞防御机制中发挥作用,包括通过NRF2.2进行自和抗氧化剂信号传递.
- NRF2 (核因子红色素2相关因子2) 是一个关键的转录因子,调节抗氧化和细胞保护基因.
研究的目的:
- 研究慢性IL-1暴露如何影响前列腺癌细胞中的p62-KEAP1复合体积累和NRF2活性.
- 为了确定慢性IL-1暴露对NRF2依赖基因在营养压力下的调节的影响.
- 阐明p62/KEAP1轴在前列腺癌细胞适应炎症条件中的作用.
主要方法:
- 长期暴露LNCaP前列腺癌细胞IL-1.
- 对NRF2目标基因 (GCLC,HMOX1) 的p62-KEAP1复合积累和mRNA水平的分析.
- 在IL-1治疗细胞中对血清饥饿的细胞反应的评估.
主要成果:
- 慢性IL-1暴露导致LNCaP细胞中p62-KEAP1复合物的高基底积累.
- 尽管p62-KEAP1高,但只有GCLC和HMOX1显示基底mRNA水平升高,表明NRF2总体活性有限.
- 暴露于IL-1的细胞对血清饥饿表现出过敏,GCLC (NRF2/KEAP1独立) 和HMOX1 (NRF2/KEAP1依赖) 的调节发生变化.
结论:
- 慢性IL-1暴露会改变前列腺癌细胞对营养压力的反应.
- 在适应慢性IL-1的细胞中,p62/KEAP1轴似乎获得了新的NRF2独立功能.
- 这些发现表明,用于管理由炎症驱动的前列腺癌进展的新治疗点.
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