PTEN以DNA甲基化依赖的方式调节其伪基因在质母细胞中的表达
Tatyana F Kovalenko1, Bhupender Yadav2, Ksenia S Anufrieva3
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Biochimie
|August 24, 2023
概括
在质母细胞瘤中,PTEN蛋白通过DNA甲基化调节IncPTENP1-S的表达. 这种长长的非编码RNA通过增加干细胞标记物和减少细胞粘附来促进癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 质母细胞瘤 (GBM) 是一种与PTEN瘤抑制器功能障碍相关的侵袭性脑癌.
- PTEN 伪基 (PTENP1) 产生 lncPTENP1-S,与 PTEN 相互连接的调节.
- 在GBM中,PTEN和PTENP1之间的精确分子相互作用在很大程度上是未知的.
研究的目的:
- 在GBM中调查PTEN和PTENP1促进体CpG岛屿的甲基化状态.
- 阐明 PTEN 和 lncPTENP1-S. 之间的监管机制.
- 确定lncPTENP1-S在GBM病原发生中的功能作用.
主要方法:
- 在患者衍生的GBM神经圈中对PTEN和PTENP1促进体中CpG岛甲基化的分析.
- 针对PTENP1 CpGI的制甲基和去甲基化.
- 对PTENP1促进体进行PTEN蛋白结合测试.
- 评估IncPTENP1-S对PTEN mRNA水平的影响.
- 对癌症干细胞标记物和细胞粘附的IncPTENP1-S功能的评估.
主要成果:
- 增加PTEN甲基化与降低PTENmRNA水平相关.
- PTENP1促进物甲基化显示与PTEN mRNA水平的反相关性.
- PTENP1 CpGI调节 lncPTENP1-S表达的 DNA 甲基化,取决于 PTEN 蛋白质的存在.
- PTEN蛋白与去甲基化PTENP1促进体结合抑制了IncPTENP1-S的表达.
- lncPTENP1-S没有影响PTEN mRNA水平,这表明PTENP1是下游目标.
- lncPTENP1-S通过上调癌症干细胞标记物和降低细胞粘附来促进GBM.
结论:
- 通过涉及PTENP1促进物甲基化的表观遗传机制,PTEN蛋白直接调节IncPTENP1-S的表达.
- 在GBM细胞中,PTENP1充当PTEN的下游目标.
- lncPTENP1-S在GBM中起着促癌作用,有助于其侵略性的表型.
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