Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis

Bo Ye, Dandan Fan, Weiwei Xiong, Min Li, Jian Yuan, Qi Jiang, Yuting Zhao, Jianxiang Lin, Jie Liu, Yilv Lv, Xiongjun Wang, Zhigang Li (), Jianzhong Su () and Yunbo Qiao ()
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Bo Ye: Shanghai Jiaotong University
Dandan Fan: Wenzhou Medical University
Weiwei Xiong: Guangzhou University
Min Li: Guangzhou University
Jian Yuan: Wenzhou Medical University
Qi Jiang: Wenzhou Medical University
Yuting Zhao: Guangzhou University
Jianxiang Lin: Guangzhou University
Jie Liu: Guangzhou University
Yilv Lv: Shanghai Jiaotong University
Xiongjun Wang: Guangzhou University
Zhigang Li: Shanghai Jiaotong University
Jianzhong Su: Wenzhou Medical University
Yunbo Qiao: Guangzhou University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract The role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24813-2

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DOI: 10.1038/s41467-021-24813-2

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