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首页> 美国卫生研究院文献>Scientific Reports >Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis
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Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis

机译：全基因组DNA甲基化分析揭示了远端和遗传甲基化在前列腺肿瘤发生发展中的作用

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Aberrant DNA methylation at promoters is often linked to tumorigenesis. But many aspects of DNA methylation remain unexplored, including the individual roles of distal and gene body methylation, as well as their collaborative roles with promoter methylation. Here we performed a MBD-seq analysis on prostate specimens classified into low, high, and very high risk group based on Gleason score and TNM stages. We identified gene sets with differential methylation regions (DMRs) in Distal, TSS, gene body and TES. To understand the collaborative roles, TSS was compared with the other three DMRs, resulted in 12 groups of genes with collaborative differential methylation patterns (CDMPs). We found several groups of genes that show opposite methylation patterns in Distal and Genic regions compared to TSS region, and in general they are differentially expressed genes (DEGs) in tumors in TCGA RNA-seq data. IPA (Ingenuity Pathway Analysis) reveals AR/TP53 signaling network to be a major signaling pathway, and survival analysis indicates genes subsets significantly associated with prostate cancer recurrence. Our results suggest that DNA methylation in Distal and Genic regions also plays critical roles in contributing to prostate tumorigenesis, and may act either positively or negatively with TSSs to alter gene regulation in tumors.
机译：启动子的异常DNA甲基化通常与肿瘤发生有关。但是，DNA甲基化的许多方面尚未探索，包括远端甲基化和基因体甲基化的个别作用，以及它们与启动子甲基化的协同作用。在此，我们根据格里森评分和TNM分期对低，高和极高风险组的前列腺标本进行了MBD-seq分析。我们确定了在远端，TSS，基因体和TES中具有差异甲基化区域（DMR）的基因集。为了了解协同作用，将TSS与其他三个DMR进行了比较，得出12组具有协同差异甲基化模式（CDMP）的基因。我们发现了几组与TSS区域相比在远端和外源区域显示相反甲基化模式的基因，并且在TCGA RNA-seq数据中，它们通常是肿瘤中的差异表达基因（DEG）。 IPA（独创性途径分析）表明AR / TP53信号网络是主要的信号途径，生存分析表明与前列腺癌复发显着相关的基因子集。我们的研究结果表明，远端和外源性区域的DNA甲基化在前列腺癌的发生中也起着关键作用，并且可能与TSS发生正相关或负相关的作用，从而改变肿瘤的基因调控。

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