MED1-driven ecDNA super-enhancers in cancer

Jiaqi Zhou; Xing Kang; Yang Zhang; Haiyun Gan

doi:10.1016/j.ccell.2025.10.011

MED1-driven ecDNA super-enhancers in cancer

Cancer Cell. 2025 Dec 8;43(12):2186-2188. doi: 10.1016/j.ccell.2025.10.011. Epub 2025 Nov 13.

Authors

Jiaqi Zhou¹, Xing Kang¹, Yang Zhang¹, Haiyun Gan²

Affiliations

¹ Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
² Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address: hy.gan@siat.ac.cn.

PMID: 41237767
DOI: 10.1016/j.ccell.2025.10.011

Abstract

Extrachromosomal circular DNA (ecDNA), enriched with enhancers, drives oncogenic transcription and tumor progression, but the mechanisms remain elusive. In this issue of Cancer Cell, Wei et al. uncover MED1-driven ecDNA super-enhancers as regulatory hubs and show that disrupting ecDNA-containing condensates selectively impairs transcription and induces apoptosis in a cancer-type-specific manner.

MeSH terms

Apoptosis / genetics
DNA, Circular* / genetics
Enhancer Elements, Genetic*
Gene Expression Regulation, Neoplastic
Humans
Mediator Complex Subunit 1* / genetics
Mediator Complex Subunit 1* / metabolism
Neoplasms* / genetics
Neoplasms* / pathology

Substances

Mediator Complex Subunit 1
DNA, Circular
MED1 protein, human