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Role of METTL3 in high glucose-induced trophoblast cell pyroptosis by the CEBPB/miR-96-5p/CCND2 axis via m6A modification

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机构： [1]Department of Gynecology and Obstetrics, Affiliated Hospital of Hebei University, Baoding, 071000, China. [2]Department of Obstetrics and Gynecology, Tiantai People's Hospital of Zhejiang Province (Tiantai Branch of Zhejiang Provincial People's Hospital), Hangzhou Medical College, Taizhou, Zhejiang, 317200, China.

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关键词： Gestational diabetes mellitus Trophoblast cells Pyroptosis METTL3 CEBPB

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Gestational diabetes mellitus (GDM) is regarded as abnormally elevated glucose contents at pregnancy period. We attempt to explore the interaction of methyltransferase 3 (METTL3) in high glucose (HG)-treated trophoblast cell pyroptosis, thereby finding a new target for GDM treatment. HTR8/SVneo cells were stimulated using HG to establish GDM models for the following assessment of METTL3, CCAAT enhancer binding protein beta (CEBPB), microRNA (miR)-96-5p and cyclin D2 (CCND2). Levels of pyroptosis-related indicators were verified. m6A level in GDM and the enrichment of m6A on CEBPB were evaluated. The binding relation between CEBPB and miR-96-5p and between miR-96-5p and CCND2 were verified. Roles of METTL3 silencing, CEBPB overexpression, miR-96-5p silencing, and CCND2 overexpression in HG-induced trophoblast cell pyroptosis were detected. METTL3, CEBPB, and CCND2 were upregulated in GDM placenta tissues and HG-induced HTR8/SVneo cells, while miR-96-5p was downregulated. Levels of pyroptosis-related indicators were upregulated, which were counteracted upon METTL3 silencing. Mechanically, METTL3-mediated m6A modification promoted CEBPB expression, inhibited miR-96-5p, which targeted CCND2. CEBPB overexpression, miR-96-5p silencing, and CCND2 could neutralize the suppressive effect of METTL3 knockdown on HG-induced trophoblast cell pyroptosis. METTL3-mediated m6A modification promoted CEBPB expression to suppressmiR-96-5p expression and promote CCND2 expression, thus strengthening HG-induced trophoblast cell pyroptosis.Copyright © 2025. Published by Elsevier Inc.

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大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

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第一作者机构： [1]Department of Gynecology and Obstetrics, Affiliated Hospital of Hebei University, Baoding, 071000, China.

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