ArticleFrontiers in genetics2023
Super enhancer-driven core transcriptional regulatory circuitry crosstalk with cancer plasticity and patient mortality in triple-negative breast cancer.
Article in Frontiers in genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Super-enhancers in immune system regulation: mechanisms, pathological reprogramming, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer. Core transcriptional regulatory circuitry (CRC) consists of autoregulated transcription factors (TFs) and their enhancers, which dominate gene expression programs and control cell fate. However, there is limited knowledge of CRC in TNBC. Herein, we systemically characterized the activated super-enhancers (SEs) and interrogated 14 CRCs in breast cancer. We found that CRCs could be broadly involved in DNA conformation change, metabolism process, and signaling response affecting the gene expression reprogramming. Furthermore, these CRC TFs are capable of coordinating with partner TFs bridging the enhancer-promoter loops. Notably, the CRC TF and partner pairs show remarkable specificity for molecular subtypes of breast cancer, especially in TNBC. USF1, SOX4, and MYBL2 were identified as the TNBC-specific CRC TFs. We further demonstrated that USF1 was a TNBC immunophenotype-related TF. Our findings that the rewiring of enhancer-driven CRCs was related to cancer immune and mortality, will facilitate the development of epigenetic anti-cancer treatment strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.