{"paper_id":"e2b7e4ff-df60-4470-8bff-b20d201f77d9","body_text":"Abstract\nEndometriosis (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.\nSimilar content being viewed by others\nData availability\nThe datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.\nAbbreviations\n- EM:\n-\nEndometriosis\n- ESCs:\n-\nendometrial stromal cells\n- FOXC1:\n-\nforkhead box C1\n- Ect-ESCs:\n-\nectopic ESCs\n- FOX:\n-\nForkhead box\n- m6A:\n-\nN6-methyladenosine\n- IGF2BPs:\n-\nInsulin-like growth factor 3 mRNA binding proteins\n- ITG:\n-\nIntegrins\n- ITGB1:\n-\nITG Integrins β 1\n- DMEM:\n-\nDulbecco’s modified Eagle medium\n- FBS:\n-\nfetal bovine serum\n- PBS:\n-\nphosphate buffer solution\n- IgG:\n-\nimmunoglobulin G\n- DAB:\n-\ndiaminobenzidine\n- siRNAs:\n-\nSmall interfering RNAs\n- ChIP:\n-\nChromatin immunoprecipitation\n- SDS:\n-\nsodium dodecyl sulfate\n- WT:\n-\nwild-type\n- MUT:\n-\nmutant\n- PCR:\n-\npolymerase chain reaction\n- RT-qPCR:\n-\nreal-time quantitative PCR\n- cDNA:\n-\ncomplementary DNA\n- GAPDH:\n-\nglyceraldehyde-3-phosphate dehydrogenase\n- SDS-PAGE:\n-\nsodium dodecyl sulfate polyacrylamide gel electrophoresis\n- ANOVA:\n-\nanalysis of variance\nReferences\nAznaurova YB, Zhumataev MB, Roberts TK, Aliper AM, Zhavoronkov AA (2014) Molecular aspects of development and regulation of endometriosis. 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Nucleic Acids Res 44(10):e91\nZhou X, Chen Z, Pei L, Sun J (2021) MicroRNA miR-106a-5p targets forkhead box transcription factor FOXC1 to suppress the cell proliferation, migration, and invasion of ectopic endometrial stromal cells via the PI3K/Akt/mTOR signaling pathway. Bioengineered 12(1):2203–2213\nAcknowledgements\nWe acknowledge investigators and participants in the study.\nFunding\nThis study was not funded.\nAuthor information\nAuthors and Affiliations\nContributions\nRH designed the study and drafted the manuscript. YL and YZ performed experiments. YL revised the manuscript. All authors read and approved of the final manuscript.\nCorresponding author\nEthics declarations\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nHuang, R., Li, Y. & Zhang, Y. Mechanism of FOXC1 in the invasion and migration of ectopic endometrial stromal cells in endometriosis. Pflugers Arch - Eur J Physiol 478, 9 (2026). https://doi.org/10.1007/s00424-025-03137-w\nReceived:\nRevised:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s00424-025-03137-w","source_license":"CC0","license_restricted":false}