Authors: 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
Published: 2021-04-14
DOI: 10.1038/s41467-021-22445-0
Source: Full article
AbstractBreast 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.