METTL14-mediated m⁶A modification regulates endometrial receptivity by inhibiting SLC39A14

Endometrial receptivity is a complex process that prepares the endometrium for embryo implantation. Inadequate endometrial receptivity is one cause of implantation failure. This study aimed to explore the impact of METTL14-mediated m⁶A modification of SLC39A14 on endometrial stromal cells (ESCs). ESCs were transfected and subjected to CCK-8 viability assay, EdU proliferation assay, and flow cytometry cell cycle and apoptosis analyses. Autophagy-related proteins LC3, p62, and Beclin-1 were detected through western blotting. RIP was used to detect the interaction between METTL14 protein and SLC39A14 mRNA. Me-RIP was used to measure the m⁶A level of SLC39A14. Actinomycin D was used to assess the stability of SLC39A14 mRNA. METTL14 overexpression or SLC39A14 knockdown enhanced viability, promoted proliferation and cell cycle progression, restrained apoptosis, reduced LC3II/LC3I and Beclin-1 levels, and increased p62 expression in ESCs. METTL14 bound to SLC39A14 mRNA and increased SLC39A14 m⁶A modification, reducing SLC39A14 mRNA stability and SLC39A14 protein expression. SLC39A14 overexpression eliminated the effect of METTL14 overexpression on ESCs. In conclusion, METTL14 promotes proliferation and inhibits apoptosis and autophagy activation in ESCs by inhibiting SLC39A14.