Enhancer RNA-mediated transcriptional regulatory programs reveal the malignant progression of glioma.

in Science advances by Yingying Ma, Shuyuan Wang, Yijie Jia, Shijie Wang, Wendian Liu, Jiaxin Yu, Jun Wang, Jingkai Geng, Jiayi Zhao, Zheng Zhao, Juan Xu, Hui Liu

TLDR

  • The study analyzed eRNA behavior in gliomas and found that eRNA-mediated regulatory rewiring contributes to glioma progression, highlighting potential therapeutic targets.
  • Drug response-related eRNAs associated with poor prognosis were identified, providing insights into glioma diagnosis and treatment monitoring.
  • Future studies can focus on investigating transcriptional mechanisms and identifying additional therapeutic targets for glioma treatment.

Abstract

To systematically investigate the molecular and pathological mechanisms of enhancer RNA (eRNA)-mediated transcriptional regulation in glioma recurrence and progression, transcriptomic, regulatome, and genomic data were integrated to analyze eRNA behavior in lower-grade gliomas (stages II/III) and glioblastomas (stage IV). Most eRNAs exhibited dynamic expression during glioma progression, regulated by master transcription factors (TFs) and affected by genomic mutations. The constructed perturbed TF-mediated eRNA-promoter regulatory landscape revealed that rewiring eRNA-promoter networks contributed to glioma malignancy. Drug response-related eRNAs associated with poor prognosis were identified, highlighting their clinical potential. Overall, integrative analysis highlights the critical role of eRNA-mediated regulatory rewiring in glioma progression, providing valuable insights into transcriptional mechanisms and potential therapeutic targets.

Overview

  • The study aimed to investigate the molecular and pathological mechanisms of enhancer RNA (eRNA)-mediated transcriptional regulation in glioma recurrence and progression.
  • Transcriptomic, regulatome, and genomic data were integrated to analyze eRNA behavior in lower-grade gliomas (stages II/III) and glioblastomas (stage IV).
  • The study aimed to identify the critical role of eRNA-mediated regulatory rewiring in glioma progression and provide valuable insights into transcriptional mechanisms and potential therapeutic targets.

Comparative Analysis & Findings

  • Most eRNAs exhibited dynamic expression during glioma progression, regulated by master transcription factors (TFs) and affected by genomic mutations.
  • The constructed perturbed TF-mediated eRNA-promoter regulatory landscape revealed that rewiring eRNA-promoter networks contributed to glioma malignancy.
  • Drug response-related eRNAs associated with poor prognosis were identified, highlighting their clinical potential.

Implications and Future Directions

  • The study highlights the critical role of eRNA-mediated regulatory rewiring in glioma progression, providing valuable insights into transcriptional mechanisms and potential therapeutic targets.
  • The identified eRNAs associated with poor prognosis can be used as potential biomarkers for glioma diagnosis and treatment monitoring.
  • Future studies can focus on further investigating the transcriptional mechanisms of glioma progression and identifying additional therapeutic targets for glioma treatment.
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