{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:09:08Z","timestamp":1784542148736,"version":"3.55.0"},"reference-count":47,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanxi Provincial Central Guidance Local Science and Technology Development Project","award":["YDZJSX2022A069"],"award-info":[{"award-number":["YDZJSX2022A069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Growing evidence indicates a significant correlation between polycystic ovary syndrome (PCOS) and endometrial carcinoma (EC); nevertheless, the fundamental molecular mechanisms involved continue to be unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Initially, differential analysis, the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to identify candidate genes associated with ferroptosis in PCOS. Subsequently, the TCGA-UCEC data were utilized to pinpoint the core gene. Then, the expression of <jats:italic>ENPP2<\/jats:italic> in granulosa cells and endometrium of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of <jats:italic>ENPP2<\/jats:italic> in the progression from PCOS to EC through western blotting (WB), colony formation assay, cell scratch assay, transwell assay, and immunofluorescence (IF). Subsequently, <jats:italic>ENPP2<\/jats:italic> gene set enrichment analysis (GSEA) analyses were conducted to identify common pathways involved in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor microenvironment (TME) were explored to examine the involvement of <jats:italic>ENPP2<\/jats:italic> in EC progression.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The datasets TCGA-UCEC (pertaining to EC), <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE34526\">GSE34526<\/jats:uri>, <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE137684\">GSE137684<\/jats:uri>, and <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE6798\">GSE6798<\/jats:uri> (related to PCOS) were procured and subjected to analysis. The gene <jats:italic>ENPP2<\/jats:italic> has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of <jats:italic>ENPP2<\/jats:italic> expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of <jats:italic>ENPP2<\/jats:italic> expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. <jats:italic>In vitro<\/jats:italic>, the WB revealed that 5-dihydrotestosterone (DHT) upregulated <jats:italic>ENPP2<\/jats:italic> expression in Ishikawa and HEC-1-A cells. Additionally, we found that <jats:italic>ENPP2<\/jats:italic> promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed <jats:italic>ENPP2<\/jats:italic> may lead to an increase in <jats:italic>CYP19A1<\/jats:italic> (aromatase) and <jats:italic>AR<\/jats:italic> mRNA level. IF demonstrated that <jats:italic>ENPP2<\/jats:italic> increased the expression of <jats:italic>AR<\/jats:italic>, suggesting a regulatory role for <jats:italic>ENPP2<\/jats:italic> in hormonal response within PCOS and EC. Our findings indicated a significant correlation between <jats:italic>ENPP2<\/jats:italic> expression and the modulation of immune responses.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18666","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T09:59:48Z","timestamp":1734688788000},"page":"e18666","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic 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