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Updated: Sep 11, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Multi-omics dissection of super-enhancer heterogeneity reveals subtype-specific transcriptional drivers in
Zhilin Lu1, Zhenchang Wang1, Wenyong Zhu1
1State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Abstract:
As a clinically heterogeneous breast cancer subtype, triple-negative breast cancer (TNBC) currently lacks effective targeted therapies. The subtype-specific heterogeneity of tumor phenotypes and gene expression programs poses challenges for the treatment of TNBC. However, while progress has been made in understanding the epigenetic and molecular mechanisms of TNBC, studies on the role of super-enhancers (SEs) in TNBC remain limited, particularly in the exploration of preclinical models at the subtype level. This study constructed a transcriptome-driven subtype classifier for cell lines, characterized epigenetic heterogeneity in the Fudan University Shanghai Cancer Center (FUSCC) TNBC subtypes, and mapped subtype-specific super-enhancers landscape. We revealed SE-mediated regulatory mechanisms underlying subtype divergence and proposed epigenetically informed therapeutic targets. We identified ZNF703 as a regulator in the LAR subtype and NesBCL11A in the BLIS subtype, both with clinical implications. This research offers new insights into TNBC's molecular mechanisms and potential targets for subtype-specific therapies.
Insights
Researchers explored super-enhancers in triple-negative breast cancer (TNBC) subtypes, identifying ZNF703 and NesBCL11A as potential therapeutic targets for specific TNBC types.
Area of Science:
- Oncology
- Genomics
- Epigenetics
Background:
- Triple-negative breast cancer (TNBC) is a heterogeneous subtype lacking targeted therapies.
- Tumor heterogeneity in TNBC presents treatment challenges.
- Limited research exists on super-enhancers (SEs) in TNBC, especially at the subtype level.
Purpose of the Study:
- To construct a transcriptome-driven subtype classifier for TNBC cell lines.
- To characterize epigenetic heterogeneity and map subtype-specific SEs in TNBC.
- To identify SE-mediated regulatory mechanisms and potential therapeutic targets.
Main Methods:
- Developed a transcriptome-driven classifier for TNBC cell line subtypes.
- Characterized epigenetic heterogeneity within FUSCC TNBC subtypes.
- Mapped subtype-specific super-enhancer landscapes.
Main Results:
- Revealed SE-mediated regulatory mechanisms driving TNBC subtype divergence.
- Identified ZNF703 as a regulator in the LAR subtype.
- Identified NesBCL11A as a regulator in the BLIS subtype, both with clinical relevance.
Conclusions:
- Super-enhancers play a crucial role in TNBC subtype divergence.
- Epigenetically informed therapeutic targets, ZNF703 and NesBCL11A, show clinical potential for specific TNBC subtypes.
- This study provides new insights into TNBC molecular mechanisms and subtype-specific therapies.
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