瘤性脂肪酸氧化感知睡眠不足增强瘤发生的昼夜干扰
Fei Peng1, Jinxin Lu1, Keyu Su2
1Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
Cell metabolism
|May 21, 2024
概括
睡眠不足会破坏昼夜节律,促进癌症. 脂肪酸氧化作为传感器,将时钟中断与癌症生长联系起来. 定时β-endorphin可能提供一种治疗策略.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 时间生物学 时间生物学
背景情况:
- 循环节障碍与癌症预后不佳有关.
- 睡眠不足增强瘤发生的机制尚未完全理解.
研究的目的:
- 为了识别参与睡眠不足增强的肺瘤发生的昼夜传感器.
- 阐明将昼夜干扰与癌症干细胞联系起来的分子机制.
主要方法:
- 进行了无偏见的转录和代谢分析.
- 研究了脂肪酸氧化 (FAO) 和相关酶的作用.
- 研究了CLOCK蛋白,ACSL1和ZDHHC5.5之间的相互作用.
主要成果:
- 脂肪酸氧化 (FAO) 被确定为睡眠不足 (SD) 引起的昼夜干扰的传感器.
- 由于CLOCK链接SD到FAO过度激活的ACSL1,增加了棕甲基辅酶A (PA-CoA).
- 一个涉及CLOCK S-palmitoylation的积极反循环稳定了CLOCK,保持了癌症干性.
- 定时的β-endorphin给药重新设置了昼夜节律,并缓解了SD增强的瘤发生.
结论:
- 粮农组织感知到的循环节障碍在睡眠不足下促进肺部瘤发生.
- 一个涉及CLOCK和ACSL1的反循环维持了癌症干性.
- 贝塔-内啡显示出作为睡眠相关癌症的长期治疗剂的潜力.
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