Aromatase inhibitor regulates let-7 expression and let-7f-induced cell migration in endometrial cells from women with endometriosis

Fertil Steril. 2016 Sep 1;106(3):673-80. doi: 10.1016/j.fertnstert.2016.05.020. Epub 2016 Jun 16.

Abstract

Objective: To evaluate associations between aromatase inhibitor (AI) treatment and let-7-family microRNA expression in endometriosis.

Design: In vitro study with the use of Ishikawa cells and human endometrial stromal cells (HESCs) obtained from patients with endometriosis.

Setting: University research center.

Patient(s): Women undergoing laparoscopic surgery for endometriosis.

Intervention(s): HESCs and Ishikawa cells treated with various letrozole concentrations and transfected with a mimic of let-7 subtypes of interest.

Main outcome measure(s): MicroRNAs let-7a-f and aromatase expression were evaluated. Migration potential after transfection with a let-7f mimic were analyzed.

Result(s): After letrozole treatment for 48 hours, all let-7 subtypes showed a trend toward increased expression in a dose-dependent manner in Ishikawa cells, and significant differences were found in let-7b and let-7f between the control and 20 μmol/L treatment groups. Furthermore, let-7f showed significant differences between the control group and 1.0 μmol/L treatment group, a typical therapeutic level, in HESCs. Transfection of a let-7f mimic decreased aromatase expression in both Ishikawa cells and HESCs and led to a significant decrease in number of migrating cells in both cell types.

Conclusion(s): AI treatment significantly increased expression of let-7f in Ishikawa cells and HESCs from patients with endometriosis; increased let-7f expression effectively reduced the migration of endometrial cells. Modulation of microRNAs involved in the pathogenesis of endometriosis may have therapeutic potential for endometriosis.

Keywords: Aromatase inhibitor; endometriosis; let-7f; microRNA.

MeSH terms

  • Aromatase / metabolism*
  • Aromatase Inhibitors / pharmacology*
  • Cell Line
  • Cell Movement / drug effects*
  • Dose-Response Relationship, Drug
  • Endometriosis / enzymology*
  • Endometriosis / genetics
  • Endometriosis / pathology
  • Endometriosis / surgery
  • Endometrium / drug effects*
  • Endometrium / enzymology
  • Endometrium / pathology
  • Endometrium / surgery
  • Estradiol / pharmacology
  • Female
  • Humans
  • Laparoscopy
  • Letrozole
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nitriles / pharmacology*
  • Signal Transduction / drug effects
  • Stromal Cells / drug effects*
  • Stromal Cells / enzymology
  • Stromal Cells / pathology
  • Time Factors
  • Transfection
  • Triazoles / pharmacology*

Substances

  • Aromatase Inhibitors
  • MicroRNAs
  • Nitriles
  • Triazoles
  • mirnlet7 microRNA, human
  • Estradiol
  • Letrozole
  • Aromatase
  • CYP19A1 protein, human