增强子
胶质瘤
癌症研究
计算生物学
生物
拷贝数变化
遗传学
转录因子
基因
基因组
作者
Jun Xiao,Xiaoyan Jin,Chunlong Zhang,Haozhe Zou,Zhenghong Chang,Nan Han,Xia Li,Yunpeng Zhang,Yongsheng Li
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2021-01-01
卷期号:11 (7): 3060-3073
被引量:6
摘要
Background: Enhancers are emerging regulatory regions controlling gene expression in diverse cancer types. However, the functions of enhancer regulatory circuit perturbations driven by copy number variations (CNVs) in malignant glioma are unclear. Therefore, we aimed to investigate the comprehensive enhancer regulatory perturbation and identify potential biomarkers in glioma. Results: We performed a meta-analysis of the enhancer centered regulatory circuit perturbations in 683 gliomas by integrating CNVs, gene expression, and transcription factors (TFs) binding. We found widespread CNVs of enhancers during glioma progression, and CNVs were associated with the perturbations of enhancer activities. In particular, the degree of perturbations for amplified enhancers was much greater accompanied by the glioma malignant progression. In addition, CNVs and enhancers cooperatively regulated the expressions of cancer-related genes. Genome-wide TF binding profiles revealed that enhancers were pervasively regulated by TFs. A network-based analysis of TF-enhancer-gene regulatory circuits revealed a core TF-gene module (58 interactions including seven genes and 14 TFs) that was associated survival of patients with glioma (p < 0.001). Finally, we validated this prognosis-associated TF-gene regulatory module in an independent cohort. In summary, our analyses provided new molecular insights for enhancer-centered transcriptional perturbation in glioma therapy. Conclusion: Integrative analysis revealed enhancer regulatory perturbations in glioma and also identified a network module that was associated with patient survival, thereby providing novel insights into enhancer-centered cancer therapy.
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