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通过MBD2/3-NuRD复杂染色体重塑来探索E6和E7瘤蛋白在宫癌发生中的作用

Alina Fudulu¹, Carmen Cristina Diaconu¹, Iulia Virginia Iancu¹

¹Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania.

|May 25, 2024

概括

人类乳头瘤病毒 (HPV) 通过表观遗传变化驱动子宫癌. 这项研究确定了NuRD复合体改变的基因,将它们与HPV感染和潜在的生物标志物实用性联系起来.

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.
分子生物学分子生物学

背景情况:

子宫癌是全球领先的恶性瘤,主要是由人类乳头瘤病毒 (HPV) 引起的.
表观遗传修饰,包括DNA甲基化和染色质改变,对于HPV感染的进展至关重要.
在这些表观遗传过程中,NuR (核细胞重塑脱酶) 复合体发挥着作用.

研究的目的:

在活性HPV16E6和E7瘤基因的背景下,研究NuRD复合组件 (MBD2和MBD3) 的全基因组结合模式.
通过NuRD复合体识别受HPV16瘤基因影响的基因.
评估这些已识别的基因作为差异化宫前体病变的生物标志物的潜力.

主要方法:

利用CaSki细胞系与shRNA用于HPV16 E6/E7沉默.
采用了ChIP-seq (染色体免疫沉测序) 来确定全基因组结合模式.
进行了qRT-PCR (定量逆转录聚合酶连锁反应) 和西斑分析,以评估基因表达和蛋白质水平.

主要成果:

通过MBD2/MBD3 NuRD复合体作用的HPV16 E6/E7瘤基因导致转录活性发生改变的几种基因被确定.
建立了这些基因,HPV感染和子宫瘤发生之间的联系.
观察到受影响的基因参与基因转录,mRNA处理和翻译调节.

结论:

这项研究阐明了NuRD复合体在HPV诱导的宫癌发生中的作用.
通过NuRD识别了由HPV16瘤基因调节的关键基因,为疾病机制提供了洞察力.
这些发现表明,已识别的基因作为宫前体病变的生物标志物的潜在实用性.

关键词:

在 ChIP-seqq.在E6和E7上,蛋白是E6和E7蛋白.这是一个HPVHPVHPV.现在的NuRD复合体是什么?染色体重塑染色体重塑的方法

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