在结肠癌中,SIRT2去乙化并降低FOXM1的表达
Baris Yildiz1, Ramazan Demirel2, Jonas J Staudacher3,4
1Department of Physiology, Institute of Health Sciences, Kafkas University, Kars, Türkiye.
Journal of biochemical and molecular toxicology
|October 19, 2024
概括
通过SIRT2去乙化FOXM1,降低了其在结肠癌中的表达. 向SIRT2为结直肠癌管理提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 叉头盒M1 (FOXM1) 是细胞增殖的关键调节剂,与各种癌症有关.
- 通过包括乙化在内的翻译后修饰来调节FOXM1活动.
- SIRT2是一种脱乙酶,可以影响蛋白质的功能和表达.
研究的目的:
- 研究SIRT2在调节结肠癌中FOXM1表达中的作用.
- 为了确定SIRT2介导的FOXM1脱甲基化是否影响结肠癌的进展.
- 探索针对结直肠癌中SIRT2-FOXM1相互作用的治疗潜力.
主要方法:
- 在90个人类结肠癌组织微阵列上进行免疫组织化学检测,以评估FOXM1和SIRT2的表达.
- 同免疫沉试验用于评估SIRT2-FOXM1在结肠癌细胞中的相互作用.
- 在体外脱乙烯化试验证实SIRT2对FOXM1.1的影响.
- 在HCT116细胞中SIRT2过度表达和淘汰实验.
主要成果:
- SIRT2在物理上与FOXM1相互作用,并在体外去乙化它.
- 在结肠癌细胞中,SIRT2过度表达会降低FOXM1的表达,而SIRT2倒置会增加其表达.
- 在人类结直肠癌样本中,高SIRT2表达与FOXM1染色负相关.
- 在显著的部分结直肠癌中,SIRT2的表达率很高.
结论:
- SIRT2 deacetylates FOXM1,导致结肠癌中的FOXM1蛋白水平降低.
- 在临床结直肠癌样本中,SIRT2和FOXM1表达之间存在负相关性.
- 通过小分子抑制剂向SIRT2活性,为结直肠癌提供了一个有前途的治疗途径.
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