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

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

    Research output: Contribution to journalArticle

    13 Scopus citations

    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.

    Original languageEnglish (US)
    Article number4562
    JournalNature communications
    Volume10
    Issue number1
    DOIs
    StatePublished - Dec 1 2019

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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    Zhang, Z., Lee, J. H., Ruan, H., Ye, Y., Krakowiak, J., Hu, Q., Xiang, Y., Gong, J., Zhou, B., Wang, L., Lin, C., Diao, L., Mills, G. B., Li, W., & Han, L. (2019). Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer. Nature communications, 10(1), [4562]. https://doi.org/10.1038/s41467-019-12543-5