Aromatase inhibitor regulates let-7 expression and let-7f-induced cell migration in endometrial cells from women with endometriosis.
To evaluate associations between aromatase inhibitor (AI) treatment and let-7-family microRNA expression in endometriosis.



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



University research center.



Women undergoing laparoscopic surgery for endometriosis.



HESCs and Ishikawa cells treated with various letrozole concentrations and transfected with a mimic of let-7 subtypes of interest.



MicroRNAs let-7a-f and aromatase expression were evaluated. Migration potential after transfection with a let-7f mimic were analyzed.



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.



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.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
SiHyun
S
Cho
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Levent
L
Mutlu
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Yuping
Y
Zhou
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut. Electronic address: hugh.taylor@yale.edu.
Hugh S
HS
Taylor
D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D010535:Laparoscopy; D000077289:Letrozole; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D035683:MicroRNAs; D009570:Nitriles; D014230:Triazoles; C487931:mirnlet7 microRNA, human; D004958:Estradiol; D000077289:Letrozole; D001141:Aromatase; C561410:CYP19A1 protein, human
Aromatase inhibitor; endometriosis; let-7f; microRNA