MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis

CONTEXT: Steroidogenic factor (SF)-1 and its downstream target genes involved in estrogen signaling are aberrantly expressed in ovarian endometriosis. OBJECTIVE: Our objective was to explore the microRNA-mediated mechanism controlling aberrant SF-1 expression in ovarian endometriosis. DESIGN: Bioinformatics analysis predicted that microRNA23a and microRNA23b (miR23a/b) target the NR5A1 3'-untranslated region. We investigated the relative expression and spatial distribution of miR23a/b and analyzed the relationship between miR23a/b and SF-1 expression in endometriotic tissues. SETTING: The study was conducted at the Department of Gynecology and Obstetrics, West China Second University Hospital of Sichuan University. PATIENTS OR OTHER PARTICIPANTS: We enrolled 23 women with American Fertility Society stage III-IV ovarian endometriosis and 15 disease-free control subjects. INTERVENTIONS: Quantitative real-time RT-PCR, in situ hybridization, cell culture, transfections, and luciferase reporter assays were used in this study. MAIN OUTCOME MEASURES: The expression of miR23a/b and SF-1, CYP19A1, and StAR mRNAs; the relationships between miRNAs and SF-1 mRNA levels; and the effect of miR23a/b on SF-1 expression were measured in normal and eutopic endometrial stromal cells (ESCs) and 293T cells. RESULTS: Both miR23a and miR23b were downregulated in ectopic and eutopic endometrium, compared with normal endometrium, and their expression was inversely correlated with NR5A1 mRNA levels. SF-1 expression was inhibited by miR23a/b overexpression in eutopic ESCs and upregulated by miR23a/b inhibition in normal ESCs. CONCLUSIONS: MiR23a and miR23b are potential biomarkers of ovarian endometriosis. This study provides a novel approach for targeting the mechanisms controlling aberrant local estrogen biosynthesis in endometriosis.