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

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Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer.
Nature Communications ( IF 14.7 ) Pub Date : 2019-10-08 , DOI: 10.1038/s41467-019-12543-5
Zhao Zhang ₁ , Joo-Hyung Lee ₁ , Hang Ruan ₁ , Youqiong Ye ₁ , Joanna Krakowiak ₁ , Qingsong Hu ₂ , Yu Xiang ₁ , Jing Gong ₁ , Bingying Zhou ₃ , Li Wang ₃ , Chunru Lin ₂ , Lixia Diao ₄ , Gordon B Mills ₅ , Wenbo Li _{1,

6} , Leng Han _{1,

6}

Affiliation

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.

中文翻译：

增强子 RNA 在癌症 eRNA 靶向治疗中的转录格局和临床应用。

增强子RNA (eRNA) 是一类从增强子转录而来的非编码RNA。尽管人们越来越认识到 eRNA 在基因转录控制中的关键作用，但 eRNA 在癌症中的系统景观和潜在功能在很大程度上仍未得到探索。在这里，我们报告了大规模患者样本和癌细胞系中多组学和药物基因组学数据的整合。我们观察到 eRNA 的癌症/谱系特异性，这可能很大程度上是由组织特异性 TF 驱动的。eRNA 通过调节靶基因（包括临床可操作基因和免疫检查点）参与多种癌症信号传导途径。它们还可能通过途径内或跨途径方式影响药物反应。我们描述了一种 eRNA NET1e 的致癌潜力和治疗可能性，支持 eRNA 靶向治疗的临床可行性。我们确定了一组临床相关的 eRNA，并开发了一个用户友好的数据门户。我们的研究揭示了 eRNA 在癌症中的转录格局和临床用途。

更新日期：2019-10-08

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