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

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

Author information

1
Department of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
2
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
3
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, PR China.
4
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
5
Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97239, USA.
6
Department of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. wenbo.li@uth.tmc.edu.
7
Center for Precision Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. wenbo.li@uth.tmc.edu.
8
Department of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. leng.han@uth.tmc.edu.
9
Center for Precision Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. leng.han@uth.tmc.edu.

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.

PMID:
31594934
DOI:
10.1038/s41467-019-12543-5
Free PMC Article

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