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

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 mu mol/L treatment groups. Furthermore, let-7f showed significant differences between the control group and 1.0 mu mol/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. (C) 2016 by American Society for Reproductive Medicine.