Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Hao, Hu, Jianyang, Maryam, Alishba, Huang, Qinghua, Zhang, Yuchen, Ramakrishnan, Saravanan, Li, Jingyu, Ma, Haiying, Ma, Victor W. S., Cheuk, Wah, So, Grace Y. K., Wang, Wei, Cho, William C. S., Zhang, Liang, Chan, Kui Ming, Wang, Xin, Chin, Y. Rebecca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046763/
https://www.ncbi.nlm.nih.gov/pubmed/33854062
http://dx.doi.org/10.1038/s41467-021-22445-0
_version_ 1783678911146622976
author Huang, Hao
Hu, Jianyang
Maryam, Alishba
Huang, Qinghua
Zhang, Yuchen
Ramakrishnan, Saravanan
Li, Jingyu
Ma, Haiying
Ma, Victor W. S.
Cheuk, Wah
So, Grace Y. K.
Wang, Wei
Cho, William C. S.
Zhang, Liang
Chan, Kui Ming
Wang, Xin
Chin, Y. Rebecca
author_facet Huang, Hao
Hu, Jianyang
Maryam, Alishba
Huang, Qinghua
Zhang, Yuchen
Ramakrishnan, Saravanan
Li, Jingyu
Ma, Haiying
Ma, Victor W. S.
Cheuk, Wah
So, Grace Y. K.
Wang, Wei
Cho, William C. S.
Zhang, Liang
Chan, Kui Ming
Wang, Xin
Chin, Y. Rebecca
author_sort Huang, Hao
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8046763
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-80467632021-04-30 Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling Huang, Hao Hu, Jianyang Maryam, Alishba Huang, Qinghua Zhang, Yuchen Ramakrishnan, Saravanan Li, Jingyu Ma, Haiying Ma, Victor W. S. Cheuk, Wah So, Grace Y. K. Wang, Wei Cho, William C. S. Zhang, Liang Chan, Kui Ming Wang, Xin Chin, Y. Rebecca Nat Commun Article 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. Nature Publishing Group UK 2021-04-14 /pmc/articles/PMC8046763/ /pubmed/33854062 http://dx.doi.org/10.1038/s41467-021-22445-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access 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, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Huang, Hao
Hu, Jianyang
Maryam, Alishba
Huang, Qinghua
Zhang, Yuchen
Ramakrishnan, Saravanan
Li, Jingyu
Ma, Haiying
Ma, Victor W. S.
Cheuk, Wah
So, Grace Y. K.
Wang, Wei
Cho, William C. S.
Zhang, Liang
Chan, Kui Ming
Wang, Xin
Chin, Y. Rebecca
Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title_full Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title_fullStr Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title_full_unstemmed Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title_short Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
title_sort defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046763/
https://www.ncbi.nlm.nih.gov/pubmed/33854062
http://dx.doi.org/10.1038/s41467-021-22445-0
work_keys_str_mv AT huanghao definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT hujianyang definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT maryamalishba definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT huangqinghua definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT zhangyuchen definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT ramakrishnansaravanan definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT lijingyu definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT mahaiying definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT mavictorws definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT cheukwah definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT sograceyk definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT wangwei definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT chowilliamcs definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT zhangliang definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT chankuiming definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT wangxin definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling
AT chinyrebecca definingsuperenhancerlandscapeintriplenegativebreastcancerbymultiomicprofiling