Elevated Histone Lactylation Mediates Ferroptosis Resistance in Endometriosis Through the METTL3‐Regulated HIF1A/HMOX1 Signaling Pathway

Zongwen Liang, Jinming Liu, Yanling Gou, Honglin Wang, Zhi Li, Yingying Cao, Huiyan Zhang, Rumeng Bai, Ruru Bai, Zongfeng Zhang
Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025 · vol. 12(31) , pp. e08220 · doi:10.1002/advs.202408220 · PMID:40492577 · PMC12376633 · W4411193123
article OA: gold CC0 ⤵ 2 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Elevated histone lactylation promotes ferroptosis resistance in endometriosis via METTL3-regulated HIF1A/HMOX1 signaling, suggesting combined inhibition of lactylation and induction of ferroptosis may be an effective therapy.

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Abstract

Endometriosis (EMs) is a chronic gynecologic condition characterized by the growth of endometrial stromal and glandular tissue outside the uterine cavity of unknown etiology. Currently, ferroptosis resistance, increased glycolysis, and increased lactate production are identified in EMs. Histone lactylation is a lactate-derived posttranslational modification that is recognized primarily for its role in epigenetic regulation. In this study, it is demonstrated that increased histone lactylation contributes to ferroptosis resistance in ectopic endometrial stromal cells (EESCs). Mechanistically, histone lactylation mediates ferroptosis resistance through the hypoxia-inducible factor 1 alpha (HIF1A)/heme oxygenase 1 (HMOX1) signaling pathway, which is regulated by methyltransferase like 3 (METTL3). In vivo experiments reveal that combination therapy with 2-deoxy-D-glucose (2-DG) and erastin is more effective for the treatment of EMs. Together, the findings provide a theoretical basis for the pathogenesis of EMs and suggest that a combined treatment that inhibits histone lactylation and induces ferroptosis is an effective treatment for EMs.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Ferroptosis Ferroptosis Ferroptosis Ferroptosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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