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

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^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

110 Citations (Scopus)

127 Downloads (CityUHK Scholars)

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.

Original language	English
Article number	2242
Journal	Nature Communications
Volume	12
Online published	14 Apr 2021
DOIs	https://doi.org/10.1038/s41467-021-22445-0
Publication status	Published - 2021

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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.

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Huang, H., Hu, J., Maryam, A., Huang, Q., Zhang, Y., Ramakrishnan, S., Li, J., Ma, H., Ma, V. W. S., Cheuk, W., So, G. Y. K., Wang, W., Cho, W. C. S., Zhang, L., Chan, K. M., Wang, X., & Chin, Y. R. (2021). Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling. Nature Communications, 12, Article 2242. https://doi.org/10.1038/s41467-021-22445-0

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title = "Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling",

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.",

author = "Hao Huang and Jianyang Hu and Alishba Maryam and Qinghua Huang and Yuchen Zhang and Saravanan Ramakrishnan and Jingyu Li and Haiying Ma and Ma, \{Victor W. S.\} and Wah Cheuk and So, \{Grace Y. K.\} and Wei Wang and Cho, \{William C. S.\} and Liang Zhang and Chan, \{Kui Ming\} and Xin Wang and Chin, \{Y. Rebecca\}",

year = "2021",

doi = "10.1038/s41467-021-22445-0",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling

AU - Huang, Hao

AU - Hu, Jianyang

AU - Maryam, Alishba

AU - Huang, Qinghua

AU - Zhang, Yuchen

AU - Ramakrishnan, Saravanan

AU - Li, Jingyu

AU - Ma, Haiying

AU - Ma, Victor W. S.

AU - Cheuk, Wah

AU - So, Grace Y. K.

AU - Wang, Wei

AU - Cho, William C. S.

AU - Zhang, Liang

AU - Chan, Kui Ming

AU - Wang, Xin

AU - Chin, Y. Rebecca

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85104328129

UR - https://www.scopus.com/pages/publications/85104328129#tab=impact

U2 - 10.1038/s41467-021-22445-0

DO - 10.1038/s41467-021-22445-0

M3 - RGC 21 - Publication in refereed journal

C2 - 33854062

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 2242

ER -

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

Abstract

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GRF: Deciphering the Molecular Mechanisms of H2BE76K Mutation in Cancer

GRF: Dissecting Age-dependent Molecular Heterogeneity of Colorectal Cancer and Establishing a Probabilistic Model for Robust Prediction of High-risk Young-onset Colorectal Cancer Patients

GRF: Elucidating the Mechanisms and Regulation of TCOF1 in the Pathogenesis of Breast Cancer

Cite this

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

Abstract

UN SDGs

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

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Projects

GRF: Deciphering the Molecular Mechanisms of H2BE76K Mutation in Cancer

GRF: Dissecting Age-dependent Molecular Heterogeneity of Colorectal Cancer and Establishing a Probabilistic Model for Robust Prediction of High-risk Young-onset Colorectal Cancer Patients

GRF: Elucidating the Mechanisms and Regulation of TCOF1 in the Pathogenesis of Breast Cancer

Cite this