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

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; Liang Zhang; Kui Ming Chan; Xin Wang; Y. Rebecca Chin

doi:10.1038/s41467-021-22445-0

Author(s)

Jianyang Hu
Qinghua Huang
Saravanan Ramakrishnan
Victor W. S. Ma
Wah Cheuk
Grace Y. K. So
Wei Wang
William C. S. Cho
Liang Zhang
Kui Ming Chan
Xin Wang
Y. Rebecca Chin

Related Research Unit(s)

Detail(s)

Original language	English
Article number	2242
Journal / Publication	Nature Communications
Volume	12
Online published	14 Apr 2021
Publication status	Published - 2021

Link(s)

DOI	DOI https://doi.org/10.1038/s41467-021-22445-0 Final Published version
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Attachment(s)	Documents 75352687.pdf Final Published version, 8.29 MB, PDF Publisher's Copyright Statement This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format.
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-85104328129&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(61baeae4-6d1a-4d18-bcb1-40efa6238119).html

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.