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Identification of Transcription Factor/Gene Axis in Colon Cancer Using a Methylome Approach.
Frontiers in Genetics ( IF 2.8 ) Pub Date : 2020-07-15 , DOI: 10.3389/fgene.2020.00864
Jiayu Zhang 1 , Bo Li 2 , Kexin Shen 3 , Huaiyu Zhang 3 , ZiJian Gong 4 , Huaqing Shi 3 , Yang Jiang 3
Affiliation  

Colon cancer is one of the most commonly diagnosed cancers worldwide. Both environmental and molecular characters can influence its development. DNA methylation has been heralded as a promising marker for use in cancer prevention, diagnosis, and treatment. It has been shown to facilitate cancer progression through multiple mechanisms. Changes in DNA methylation can inhibit or promote the binding of transcription factors (TFs) and further disturb gene regulation. Detection of DNA methylation-mediated regulatory events in colon cancer are critical for mining novel biomarkers. Here, we explore the influence of CpG sites located at promoter regions of differentially expressed genes and identify methylation–gene relationships using expression–methylation quantitative trait loci. We find that promoter methylation sites mainly negatively regulate the corresponding genes. We also identify candidate TFs that can bind to these sites in a sequence-dependent manner. By integrating transcriptome and methylome profiles, we construct a TF–CpG–gene regulatory network for colon cancer, which is used to determine the roles of TFs and methylation in the transcription process. Finally, based on TF–CpG–gene relationships, we design a framework to evaluate patient prognosis, which shows that one TF–CpG–gene triplet is significantly associated with patient survival rate and represents a potential novel biomarker for use in colon cancer prognosis and treatment.



中文翻译:

使用甲基化组方法鉴定结肠癌中的转录因子/基因轴。

结肠癌是全球最常被诊断的癌症之一。环境和分子特性均可影响其发展。DNA甲基化被认为是用于癌症预防,诊断和治疗的有前途的标志物。已经显示出它可以通过多种机制促进癌症的进展。DNA甲基化的变化可以抑制或促进转录因子(TFs)的结合,并进一步干扰基因调控。结肠癌中DNA甲基化介导的调控事件的检测对于挖掘新型生物标志物至关重要。在这里,我们探讨了位于差异表达基因启动子区域的CpG位点的影响,并使用表达-甲基化定量性状基因座鉴定了甲基化与基因的关系。我们发现启动子甲基化位点主要是负调控相应的基因。我们还确定了可以与序列依赖的方式绑定到这些网站的候选TF。通过整合转录组和甲基化组图谱,我们构建了结肠癌的TF-CpG-基因调控网络,该网络用于确定TF和甲基化在转录过程中的作用。最后,基于TF-CpG-基因之间的关系,我们设计了一个评估患者预后的框架,该框架表明一个TF-CpG-基因三联体与患者生存率显着相关,并且代表了一种可能用于结肠癌预后的新型生物标志物。治疗。我们为结肠癌构建了TF–CpG–基因调控网络,该网络用于确定TF和甲基化在转录过程中的作用。最后,基于TF-CpG-基因之间的关系,我们设计了一个评估患者预后的框架,该框架表明一个TF-CpG-基因三联体与患者生存率显着相关,并且代表了一种可能用于结肠癌预后的新型生物标志物。治疗。我们为结肠癌构建了TF–CpG–基因调控网络,该网络用于确定TF和甲基化在转录过程中的作用。最后,基于TF-CpG-基因之间的关系,我们设计了一个评估患者预后的框架,该框架表明一个TF-CpG-基因三联体与患者生存率显着相关,并且代表了一种可能用于结肠癌预后的新型生物标志物。治疗。

更新日期:2020-07-31
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