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Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling

Author

Listed:
  • Hao Huang

    (City University of Hong Kong)

  • Jianyang Hu

    (City University of Hong Kong
    City University of Hong Kong)

  • Alishba Maryam

    (City University of Hong Kong)

  • Qinghua Huang

    (Guangxi Medical University)

  • Yuchen Zhang

    (City University of Hong Kong)

  • Saravanan Ramakrishnan

    (City University of Hong Kong)

  • Jingyu Li

    (City University of Hong Kong
    City University of Hong Kong)

  • Haiying Ma

    (City University of Hong Kong
    City University of Hong Kong)

  • Victor W. S. Ma

    (Queen Elizabeth Hospital)

  • Wah Cheuk

    (Queen Elizabeth Hospital)

  • Grace Y. K. So

    (Queen Elizabeth Hospital)

  • Wei Wang

    (City University of Hong Kong)

  • William C. S. Cho

    (Queen Elizabeth Hospital)

  • Liang Zhang

    (City University of Hong Kong
    City University of Hong Kong)

  • Kui Ming Chan

    (City University of Hong Kong
    City University of Hong Kong)

  • Xin Wang

    (City University of Hong Kong
    City University of Hong Kong)

  • Y. Rebecca Chin

    (City University of Hong Kong
    City University of Hong Kong)

Abstract

Breast cancer is a heterogeneous disease, affecting over 3.5 million women worldwide, yet the functional role of cis-regulatory elements including super-enhancers in different breast cancer subtypes remains poorly characterized. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. Here we apply integrated epigenomic and transcriptomic profiling to uncover super-enhancer heterogeneity between breast cancer subtypes, and provide clinically relevant biological insights towards TNBC. Using CRISPR/Cas9-mediated gene editing, we identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1 and MET, thereby unveiling a mechanism for specific overexpression of the key oncogenes in TNBC. We also identify ANLN as a TNBC-specific gene regulated by super-enhancer. Our studies reveal a TNBC-specific epigenomic landscape, contributing to the dysregulated oncogene expression in breast tumorigenesis.

Suggested Citation

  • Hao Huang & Jianyang Hu & Alishba Maryam & Qinghua Huang & Yuchen Zhang & Saravanan Ramakrishnan & Jingyu Li & Haiying Ma & Victor W. S. Ma & Wah Cheuk & Grace Y. K. So & Wei Wang & William C. S. Cho , 2021. "Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22445-0
    DOI: 10.1038/s41467-021-22445-0
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