Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer

Nat Commun. 2019 Oct 8;10(1):4562. doi: 10.1038/s41467-019-12543-5.


Enhancer RNA (eRNA) is a type of noncoding RNA transcribed from the enhancer. Although critical roles of eRNA in gene transcription control have been increasingly realized, the systemic landscape and potential function of eRNAs in cancer remains largely unexplored. Here, we report the integration of multi-omics and pharmacogenomics data across large-scale patient samples and cancer cell lines. We observe a cancer-/lineage-specificity of eRNAs, which may be largely driven by tissue-specific TFs. eRNAs are involved in multiple cancer signaling pathways through putatively regulating their target genes, including clinically actionable genes and immune checkpoints. They may also affect drug response by within-pathway or cross-pathway means. We characterize the oncogenic potential and therapeutic liability of one eRNA, NET1e, supporting the clinical feasibility of eRNA-targeted therapy. We identify a panel of clinically relevant eRNAs and developed a user-friendly data portal. Our study reveals the transcriptional landscape and clinical utility of eRNAs in cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Datasets as Topic
  • Drug Screening Assays, Antitumor
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks / drug effects
  • Genomics
  • Humans
  • Inhibitory Concentration 50
  • Molecular Targeted Therapy / methods
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Oncogene Proteins / genetics
  • Promoter Regions, Genetic
  • RNA, Untranslated / antagonists & inhibitors*
  • RNA, Untranslated / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects*


  • Antineoplastic Agents
  • NET1 protein, human
  • Oncogene Proteins
  • RNA, Untranslated
  • Transcription Factors