The miR-25-3p/Sp1 pathway is dysregulated in ovarian endometriosis.

Abstract

ObjectiveThe transcription factor Specificity protein 1 (Sp1) plays important roles in many critical biological functions; however, its expression and underlying functions in endometriosis remain undefined. Bioinformatics has suggested that Sp1 is potentially regulated by miR-25-3p. This study investigated Sp1 and miR-25-3p expression and their interaction during the pathogenesis of endometriosis.MethodsFifteen women with American Fertility Society stage III/IV ovarian endometriosis and 14 disease-free controls were included. Sp1 expression was detected by qPCR, immunohistochemistry, and western blotting. Using both bioinformatics and genetics, we identified that Sp1 was a potential target of miR-25-3p. Then, the relationship between miR-25-3p and Sp1 was investigated by knockdown and overexpression experiments.ResultsSp1 mRNA and protein levels were increased in ectopic and eutopic endometrium compared with normal endometrium samples, with the highest expression in ectopic endometrium samples. In vitro experiments and luciferase reporter assays demonstrated that Sp1 was upregulated when miR-25-3p was depleted and that Sp1 was a direct target of miR-25-3p, respectively.ConclusionsOur study revealed increased Sp1 expression in ovarian endometriosis and subsequently demonstrated that miR-25-3p directly targets Sp1. This suggests a novel miRNA/Sp1 pathway in the pathogenesis of endometriosis, which should be further explored for other potential therapeutic targets.