REVIEW article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1610579
Super-enhancer DNA methylation in cancer: The mechanism of action and therapeutic directions
Provisionally accepted
- Yantaishan Hospital, Yantai, China
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Abstract: The interplay between DNA methylation and super-enhancer activity is emerging as a key focus in cancer research. Super-enhancers, a specialized class of enhancers, strongly activate transcription of their target genes due to their dense clustering with essential transcription factors (TFs) and cofactors. In cancer, especially, these super-enhancers control key oncogenic drivers and often display abnormal DNA methylation patterns that can repress or overexpress target genes in both solid and blood cancers. Furthermore, DNA methylation in the super-enhancer region has been found to influence their regulatory capacity. Although enhancers are typically characterized by low DNA methylation, dysregulated methylation at super-enhancers is seen in most malignancies, affecting TF and chromatin regulator recruitment. Hypomethylation at these sites often accompanies oncogene hyperactivation, while hypermethylation can repress tumor suppressor mechanisms. Recent research highlights DNA methylation as a promising source of cancer biomarkers. This review examines the intricate relationship between DNA methylation and super-enhancer activity in cancer, concentrating on how methylation regulates super-enhancers, modulates oncogene expression, promotes oncogenesis, and serves as a target for novel oncology therapies.
Keywords: super-enhancer, DNA Methylation, Cancer, metastasis, tumor immunity, biomarker
Received: 12 Apr 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Bi, Zou and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ke Wang, wangke7775@163.com
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