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

被引：118

作者：

Zhang, Zhao ^{[1
]}

Lee, Joo-Hyung ^{[1
]}

Ruan, Hang ^{[1
]}

Ye, Youqiong ^{[1
]}

Krakowiak, Joanna ^{[1
]}

Hu, Qingsong ^{[2
]}

Xiang, Yu ^{[1
]}

Gong, Jing ^{[1
]}

Zhou, Bingying ^{[3
,4
]}

Wang, Li ^{[3
,4
]}

Lin, Chunru ^{[2
]}

Diao, Lixia ^{[5
]}

Mills, Gordon B. ^{[6
]}

Li, Wenbo ^{[1
,7
]}

Han, Len ^{[1
,7
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, McGovern Med Sch, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[3] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China

[4] Peking Union Med Coll, Beijing 100037, Peoples R China

[5] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[6] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[7] Univ Texas Hlth Sci Ctr Houston, Ctr Precis Hlth, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

BREAST-CANCER; GENOME; EXPRESSION; ENCYCLOPEDIA; SENSITIVITY; ACTIVATION; FEATURES; ATLAS;

D O I：

10.1038/s41467-019-12543-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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