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Review
. 2025 Sep;480(9):5009-5028.
doi: 10.1007/s11010-025-05316-w. Epub 2025 May 28.

Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation

Limei Chen #  1 , Zhihui Wu #  2 , Weixi Yuan  3 , Nan Chen  2 , Peina Lin  2 , Senyi Liao  3 , Guopeng Xie  4
Affiliations
Review

Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation

Limei Chen et al. Mol Cell Biochem. 2025 Sep.

Abstract

Advancements in tumor research have highlighted the potential of epigenetic therapies as a targeted approach to cancer treatment. However, the application of these therapies has faced challenges due to the issue of substrate availability since the discovery of epigenetic modifications. Interestingly, metabolic changes are closely associated with epigenetic changes, and notably, certain metabolic enzymes exhibit nuclear localization within epigenetically active cellular contexts. This suggests that nuclear localization of metabolic enzymes may provide a mechanistic foundation for addressing substrate availability issues in epigenetic regulation. To date, there has been limited progress in synthesizing this information systematically. In this study, we provide an overview of the interplay between metabolic enzymes and epigenetic mechanisms, highlighting their critical roles. Subsequently, we summarize recent advances regarding the nuclear localization of metabolic enzymes, shedding light on their emerging roles in epigenetic regulation and oncogenesis.

Keywords: DNA demethylation; Epigenetic modifications; Histone modifications; Lactylation; Nuclear localization of metabolic enzymes.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study did not involve the participation of human or animal subjects, and, therefore, was exempt from formal assessment by the ethics committee for clinical research of our center. Consent for publication: Not applicable.

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