CircABCC1 reduces endometrial receptivity via METTL3/FAM155B axis.

Abstract

Objective: Impaired endometrial receptivity is the main cause of embryo implantation failure. Little information is available on the role of circRNAs in endometrial receptivity. Here, the effect of circABCC1 on endometrial receptivity and its mechanism were investigated.

Methods: GEO database was screened for key biomarkers for recurrent implantation failure (RIF). Endometrial epithelial cells (EECs) were cultured and transfected with circABCC1- and/or FAM155B-related vectors, followed by CCK-8 detection of cell proliferation, western blotting detection of receptivity-related factors LIF and DKK1, and ELISA detection of LIF secretion. An in vitro adhesion model was established to detect trophoblast adhesion to EECs. RIP was used to detect the binding of METTL3 to circABCC1 and FAM155B mRNA, and MeRIP-qPCR was used to detect m⁶A modification of FAM155B mRNA.

Results: CircABCC1 and FAM155B were highly expressed in patients with RIF. CircABCC1 or FAM155B overexpression reduced EEC proliferation, LIF and DKK1 expression, LIF secretion, and trophoblast adhesion; circABCC1 or FAM155B knockdown led to the opposite results. CircABCC1 and METTL3 positively regulated FAM155B expression. METTL3 bound circABCC1 and FAM155B mRNA. METTL3 overexpression increased m⁶A modification of FAM155B mRNA. FAM155B overexpression partially eliminated circABCC1 knockdown-induced promotion of EEC proliferation, LIF and DKK1 expression, LIF secretion, and trophoblast adhesion.

Conclusion: CircABCC1 binds to METTL3 to regulate FAM155B mRNA modification and promote FAM155B expression, thereby inhibiting EEC proliferation and reducing endometrial receptivity.