AMPK缺乏会增加DNA甲基化,并加剧AOM/DSS小鼠的结肠直肠瘤发生
Qi Sun1, Qiyu Tian1, Alejandro Bravo Iniguez1
1School of Food Science, Washington State University, Pullman, WA 99164, USA.
Genes
|July 27, 2024
概括
AMP激活蛋白激酶 (AMPK) 缺乏通过减少α-甲酸盐和促进瘤抑制基因的表观遗传变化,加速结直肠癌 (CRC) 的发展.
科学领域:
- 在瘤学瘤学.
- 代谢疾病 代谢疾病
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 大肠直肠癌 (CRC) 的发病率与代谢性疾病相关.
- AMP激活蛋白激酶 (AMPK) 在癌症代谢重编程中发挥作用.
研究的目的:
- 研究AMPK在结肠炎相关结直肠癌中的作用.
- 阐明AMPK缺乏影响CRC发育的分子机制.
主要方法:
- 在野生型和AMPK淘汰赛小鼠中诱导了氧甲/德克斯硫酸盐 (AOM/DSS) 的CRC.
- 建立了一个稳定的AMPK缺陷Caco-2细胞系用于机制研究.
- 评估瘤发育,α-甲酸盐水平,TET2转录,MLH1蛋白和Mlh1 CpG岛甲基化.
主要成果:
- AMPK缺乏加速了CRC的发展,增加了瘤的数量和大小.
- AMPK损失降低了α-甲酸盐的产生和TET2的转录,与MLH1蛋白减少相关.
- AMPK缺乏导致Mlh1高甲基化和不匹配修复/瘤抑制基因的下调.
结论:
- AMPK缺乏通过减少α-甲酸盐和增加瘤抑制基因的表观遗传沉默来促进结直肠瘤发生.
- 向AMPK可能为CRC预防和治疗提供战略.
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