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

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.