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

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.