Mechanism of FOXC1 in the invasion and migration of ectopic endometrial stromal cells in endometriosis.

Endometriosis (EM) is a common and challenging condition of reproductive-aged women and its pathogenesis is associated with endometrial stromal cells (ESCs). This study aimed to explore the role of FOXC1 in invasion and migration of ectopic ESCs (Ect-ESCs) in EM. Human eutopic and Ect-ESCs were isolated and identified, followed by detection of the levels of FOXC1, IGF2BP3, and m6A in ITGB1 in eutopic and Ect-ESCs. After interfering with FOXC1 in Ect-ESCs, cell invasion and migration were assessed. RNA immunoprecipitation assay was conducted to investigate the enrichment of IGF2BP3 or m6A on ITGB1. ITGB1 mRNA stability was examined. The roles of IGF2BP3 or ITGB1 in the invasion and migration of Ect-ESCs were verified by combined experiments. We found that FOXC1, IGF2BP3, and ITGB1 were upregulated in Ect-ESCs. FOXC1 downregulation inhibited invasion and migration of Ect-ESCs. Mechanically, FOXC1 bound to the IGF2BP3 promoter to positively regulate IGF2BP3 expression, promoted ITGB1 mRNA stability in an m6A-dependent manner, and increased ITGB1 transcription. Overexpression of IGF2BP3 or ITGB1 attenuated the inhibitory role of FOXC1 downregulation in invasion and migration of Ect-ESCs. In conclusion, FOXC1 promoted IGF2BP3 expression and stabilized ITGB1 mRNA in an m6A-dependent manner, thus promoting invasion and migration of Ect-ESCs.