Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.

Abstract

Lactic acid modification of histones represents an emerging post-translational modification that establishes a critical link between cellular metabolic reprogramming and epigenetic regulation through the covalent binding of lactic acid to histone lysine residues. In recent years, the mechanisms underlying this modification in the pathogenesis of various diseases have been progressively elucidated, revealing its extensive biological impact and potential clinical translational value. As research progresses, the functional role of histone lactylation in gynecological diseases has become increasingly evident, offering a novel epigenetic perspective for deciphering the pathogenesis of gynecological-related disorders. This review outlines the mechanisms underlying histone lactylation and focuses on its regulatory role in common benign and malignant gynecological diseases. The malignant diseases discussed include ovarian, endometrial, and cervical cancers, while the benign conditions include endometriosis and polycystic ovary syndrome. Furthermore, it undertakes an analysis of the therapeutic potential of histone lactylation modifications and reviews emerging targeted therapeutic strategies. These include targeting lactate production, lactate transport, lactylation-associated enzymes, or downstream effectors, highlighting their potential to intervene in disease progression. The present study aims to systematically elucidate the core value of histone lactylation as a novel epigenetic link between metabolism and gynecological disease pathogenesis. In addition, it provides clear research directions and robust theoretical support for developing targeted therapeutic strategies based on lactylation modifications.