1. Cancer Biology
  2. Chromosomes and Gene Expression

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

  1. Ibrahim Ahmed
  2. Shen-Hsi Yang
  3. Samuel Ogden
  4. Wei Zhang
  5. Yaoyong Li
  6. The OCCAMS Consortium
  7. Andrew D Sharrocks  Is a corresponding author
  1. University of Manchester, United Kingdom
https://doi.org/10.7554/eLife.80840
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  1. Ibrahim Ahmed
  2. Shen-Hsi Yang
  3. Samuel Ogden
  4. Wei Zhang
  5. Yaoyong Li
  6. The OCCAMS Consortium
  7. Andrew D Sharrocks
(2023)
eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
eLife 12:e80840.
https://doi.org/10.7554/eLife.80840
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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.

Data availability

All data have been deposited at ArrayExpress; OE19 KAS-seq and CUT&TAG data (E-MTAB-11357 and E-MTAB-11356, respectively) and OE19 HiC data (E-MTAB-12664).

The following data sets were generated
The following previously published data sets were used

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Author details

  1. Ibrahim Ahmed

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7424-6658

  2. Shen-Hsi Yang

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Samuel Ogden

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0217-881X

  4. Wei Zhang

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  5. Yaoyong Li

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. The OCCAMS Consortium

  7. Andrew D Sharrocks

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    For correspondence
    andrew.d.sharrocks@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7395-9552

Funding

Medical Research Council (MR/V010263/1)

  • Samuel Ogden

Wellcome Trust (102171/B/13/Z)

  • Ibrahim Ahmed

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Ahmed et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ibrahim Ahmed
  2. Shen-Hsi Yang
  3. Samuel Ogden
  4. Wei Zhang
  5. Yaoyong Li
  6. The OCCAMS Consortium
  7. Andrew D Sharrocks
(2023)
eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
eLife 12:e80840.
https://doi.org/10.7554/eLife.80840

Share this article

https://doi.org/10.7554/eLife.80840

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