Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling.
Animals
Cell Line, Tumor
Enhancer Elements, Genetic
Female
Forkhead Transcription Factors
/ genetics
Gene Editing
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Mice, Nude
Microfilament Proteins
/ genetics
Proto-Oncogene Proteins c-met
/ genetics
Triple Negative Breast Neoplasms
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 04 2021
14 04 2021
Historique:
received:
21
08
2020
accepted:
09
03
2021
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
12
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33854062
doi: 10.1038/s41467-021-22445-0
pii: 10.1038/s41467-021-22445-0
pmc: PMC8046763
doi:
Substances chimiques
ANLN protein, human
0
FOXC1 protein, human
0
Forkhead Transcription Factors
0
Microfilament Proteins
0
MET protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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