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

Author

Listed:
  • Zhao Zhang

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Joo-Hyung Lee

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Hang Ruan

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Youqiong Ye

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Joanna Krakowiak

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Qingsong Hu

    (The University of Texas MD Anderson Cancer Center)

  • Yu Xiang

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Jing Gong

    (McGovern Medical School at The University of Texas Health Science Center at Houston)

  • Bingying Zhou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Li Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Chunru Lin

    (The University of Texas MD Anderson Cancer Center)

  • Lixia Diao

    (The University of Texas MD Anderson Cancer Center)

  • Gordon B. Mills

    (Oregon Health and Science University)

  • Wenbo Li

    (McGovern Medical School at The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston)

  • Leng Han

    (McGovern Medical School at The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston)

Abstract

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.

Suggested Citation

  • Zhao Zhang & Joo-Hyung Lee & Hang Ruan & Youqiong Ye & Joanna Krakowiak & Qingsong Hu & Yu Xiang & Jing Gong & Bingying Zhou & Li Wang & Chunru Lin & Lixia Diao & Gordon B. Mills & Wenbo Li & Leng Han, 2019. "Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12543-5
    DOI: 10.1038/s41467-019-12543-5
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    Cited by:

    1. Mei Luo & Lin Ye & Ruimin Chang & Youqiong Ye & Zhao Zhang & Chunjie Liu & Shengli Li & Ying Jing & Hang Ruan & Guanxiong Zhang & Yi He & Yaoming Liu & Yu Xue & Xiang Chen & An-Yuan Guo & Hong Liu & L, 2022. "Multi-omics characterization of autophagy-related molecular features for therapeutic targeting of autophagy," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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