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

J Clin Endocrinol Metab. 2013 Apr;98(4):1575-82. doi: 10.1210/jc.2012-3010. Epub 2013 Feb 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Epigenetic Repression / genetics
  • Estrogens / metabolism
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation / physiology
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Ovarian Diseases / genetics*
  • Ovarian Diseases / metabolism
  • Ovarian Diseases / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Steroidogenic Factor 1 / genetics*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transfection
  • Up-Regulation / genetics
  • Up-Regulation / physiology
  • Young Adult

Substances

  • Estrogens
  • MIRN23a microRNA, human
  • MicroRNAs
  • Steroidogenic Factor 1