在黑色素瘤中,PRAME表达通过TET2介导的DNA基甲基化来负面调节
Rui Fang1, Tuulia Vallius2,3, Arianna Zhang4
1Department of Medicine, Brigham and Women's Hospital; Harvard Medical School, Boston MA 02115.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
在黑色素瘤中优先表达的抗原 (PRAME) 是由十-十一转位 (TET) 氧化酶介导的5-基甲基细胞素 (5hmC) 进行表观遗传调节的. TET2介导的DNA基甲基化与PRAME表达相反相关,影响黑色素瘤的发展.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 皮肤病学 皮肤病学
背景情况:
- 在黑色素瘤中优先表达的抗原 (PRAME) 和5-基甲基细胞素 (5hmC) 是新兴的黑色素瘤生物标志物.
- 在黑色素瘤进展阶段之间存在PRAME和5hmC水平之间的反向相关性.
研究的目的:
- 研究PRAME表达和TET二氧化原酶介导的5hmC在黑色素瘤中的调控关系.
- 阐明表观遗传重编程在黑色素瘤瘤发生中的作用.
主要方法:
- 免疫组织化学和多重免疫光学评估PRAME和5hmC.
- 黑色素瘤前体的单细胞成像.
- 对TCGA和GTEx数据库的生物信息分析.
- 在体外实验涉及TET2在黑色素瘤细胞系中的过度表达.
主要成果:
- 良性瘤显示高5hmC和低PRAME,而黑色素瘤则呈现相反的模式.
- 减少的5hmC与前恶性细胞中PRAME上调相关.
- 在黑色素瘤中,TET2 mRNA表达与PRAME mRNA表达有负相关.
- 在黑色素瘤中,PRAME促进体的5hmC水平降低,通过TET2恢复5hmC会降低PRAME的表达.
结论:
- 通过TET2介导的DNA基甲基化在黑色素瘤中表观遗传调节PRAME表达.
- 涉及5hmC和PRAME的表观遗传重编程是黑色素瘤发展的关键.
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