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eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways

Ibrahim Ahmed, Shen-Hsi Yang, Samuel Ogden, Wei Zhang, Yaoyong Li, the OCCAMS consortium, Andrew D. Sharrocks
doi: https://doi.org/10.1101/2022.05.11.491502
Ibrahim Ahmed
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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Shen-Hsi Yang
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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Samuel Ogden
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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Wei Zhang
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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Yaoyong Li
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Andrew D. Sharrocks
1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
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  • For correspondence: andrew.d.sharrocks@manchester.ac.uk
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Abstract

Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett’s oesophagus (BO) coupled with open chromatin maps to identify potential enhancer RNAs (eRNAs) and their associated enhancer regions in this cancer. We identify ∼1000 OAC-specific enhancers and use this data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2 and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 11, 2022.
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eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
Ibrahim Ahmed, Shen-Hsi Yang, Samuel Ogden, Wei Zhang, Yaoyong Li, the OCCAMS consortium, Andrew D. Sharrocks
bioRxiv 2022.05.11.491502; doi: https://doi.org/10.1101/2022.05.11.491502
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eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
Ibrahim Ahmed, Shen-Hsi Yang, Samuel Ogden, Wei Zhang, Yaoyong Li, the OCCAMS consortium, Andrew D. Sharrocks
bioRxiv 2022.05.11.491502; doi: https://doi.org/10.1101/2022.05.11.491502

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