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

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-06-06 DOI:10.1126/sciadv.adu9487

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

{"title":"Enhancer RNA–mediated transcriptional regulatory programs reveal the malignant progression of glioma","authors":"Yingying Ma, Shuyuan Wang, Yijie Jia, Shijie Wang, Wendian Liu, Jiaxin Yu, Jun Wang, Jingkai Geng, Jiayi Zhao, Zheng Zhao, Juan Xu, Hui Liu","doi":"10.1126/sciadv.adu9487","DOIUrl":null,"url":null,"abstract":"<div >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.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 23","pages":""},"PeriodicalIF":11.7000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu9487","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.adu9487","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

增强子rna介导的转录调控程序揭示胶质瘤的恶性进展

为了系统地研究增强子RNA （enhancer RNA, eRNA）介导的转录调控在胶质瘤复发和进展中的分子和病理机制，我们整合了转录组学、调节组学和基因组学数据，分析了eRNA在低级别胶质瘤（II/III期）和胶质母细胞瘤（IV期）中的行为。大多数erna在胶质瘤进展过程中表现出动态表达，受主转录因子（TFs）调控并受基因组突变影响。构建的受干扰的tf介导的rna启动子调控景观揭示了重新连接的rna启动子网络有助于胶质瘤恶性肿瘤。发现了与预后不良相关的药物反应相关的erna，突出了它们的临床潜力。总的来说，综合分析强调了rna介导的调节重布线在胶质瘤进展中的关键作用，为转录机制和潜在的治疗靶点提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.