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 () and Leng Han ()
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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
Leng Han: McGovern Medical School at The University of Texas Health Science Center at Houston

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12543-5

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