Mechanism of FBXW7 mRNA degradation mediated by circSMAD2 through METTL3-METTL14 m6A axis affects proliferation and invasion of endometrial stromal cells

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology Pub Date : 2025-03-22 DOI:10.1016/j.jri.2025.104523

Yuan Peng, Ping Wang, Yanqin Lou, Donghua Wang

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引用次数: 0

Abstract

This study investigates the role of circSMAD2 in ectopic endometrium of endometriosis (EMS) patients, focusing on its upregulation of FBXW7 m6A level by mediating the formation of the METTL3/METTL14 complex. Ectopic endometria from EMS patients and healthy individuals were compared for the expression levels of FBXW7 and YTHDF2, as well as total m6A levels. Results showed elevated FBXW7 and reduced YTHDF2 expressions in EMS ectopic endometria, along with decreased m6A levels. YTHDF2 was found to bind to FBXW7 mRNA, leading to its degradation and suppression of FBXW7 expression. CircSMAD2 interacted with METTL3/METTL14 complex in human endometrial stromal cells, increasing FBXW7 m6A level without affecting complex expression levels. Overexpression of YTHDF2 or circSMAD2 inhibited cell proliferation, migration, and invasion, effects partly reversed by FBXW7 overexpression. Reduced circSMAD2 expression in EMS resulted in decreased METTL3/METTL14 complex formation and FBXW7 m6A levels, while decreased YTHDF2 expression in EMS led to higher FBXW7 expression, promoting cell proliferation and invasion. This study sheds light on the regulatory mechanism of circSMAD2 in EMS pathogenesis.

Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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来源期刊

Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.30

自引率

5.90%

发文量

162

审稿时长

10.6 weeks

期刊介绍： Affiliated with the European Society of Reproductive Immunology and with the International Society for Immunology of Reproduction The aim of the Journal of Reproductive Immunology is to provide the critical forum for the dissemination of results from high quality research in all aspects of experimental, animal and clinical reproductive immunobiology. This encompasses normal and pathological processes of: * Male and Female Reproductive Tracts * Gametogenesis and Embryogenesis * Implantation and Placental Development * Gestation and Parturition * Mammary Gland and Lactation.