In:
Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-04-14)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-1723
DOI:
10.1038/s41467-021-22445-0
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2021
ZDB Id:
2553671-0
