N6-methyladenosine regulated FZD7 inhibits ferroptosis in endometriosis via β-catenin/SLC7A11 pathway

Jianyun Huang, Huang J, Shi W, Wen Shi, Liao Z, Zhouzhou Liao, Minyi Wang, Wang M, Qiyu Zhong, Zhong Q, Qiu L, Lingbing Qiu, Zhuang Jin, Jin Z, Li X, Xiao Li, Li J, Jinbo Li, Shuqin Chen, Chen S
Free radical biology & medicine · 2025 · vol. 243 , pp. 54–66 · doi:10.1016/j.freeradbiomed.2025.11.020 · PMID:41241001 · W4416261590
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study investigates how N6-methyladenosine modification of FZD7 inhibits ferroptosis in endometriosis by impacting the β-catenin/SLC7A11 pathway.

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Abstract

Endometriosis (EMS), a chronic inflammatory disease affecting approximately 10 % reproductive aged women, remains etiologically unclear. This study aims to investigate the role and underlying mechanisms of frizzled class receptor 7 (FZD7) in EMS. In vitro, cellular transfection with siRNA or plasmid constructs was employed to modulate FZD7 expression and assess its functional significance. In vivo, an EMS mouse model was established via intraperitoneal injection of endometrial fragments; therapeutic effects of FZD7 inhibition were evaluated using specific inhibitors. FZD7 inhibition significantly promoted the overproduction of reactive oxygen species (ROS) in EMS ectopic cells, increased the level of lipid peroxidation, promoted intracellular Fe2+ accumulation, and altered mitochondrial morphology. Mechanistic studies showed that decreased expression of methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) in EMS led to decreased m6A modification level, decreased degradation, and increased expression in FZD7 mRNA, and caused increased transcription of solute carrier family 7 member 11 (SLC7A11) via β-catenin, which in turn inhibited ferroptosis. We found that inhibition of FZD7 promotes ferroptosis, and that the combination of the FZD7 inhibitor (F7H) and the ferroptosis activator (erastin) in mice most significantly inhibited the progression of EMS.

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Condition tags

endometriosis

MeSH descriptors

Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine Adenosine

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