HMGA2-induced epithelial-mesenchymal transition is reversed by let-7d in intrauterine adhesions

Intrauterine adhesions (IUAs), the leading cause of uterine infertility, are characterized by endometrial fibrosis. The management of IUA is challenging because the pathogenesis of the disease largely unknown. In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P< 0.0001) and 5-fold (P = 0.0095) in the endometrial epithelial cells (EECs) of IUA patients (n = 18) compared to controls. In vivo and in vitro models of endometrial fibrosis also confirmed the overexpression of HMGA2 in EECs. In vitro cell experiments indicated that overexpression of HMGA2 promoted the epithelial-mesenchymal transition (EMT) while knockdown of HMGA2 reversed transforming growth factor-beta-induced EMT. A dual luciferase assay confirmed let-7d microRNA downregulated HMGA2 and repressed the pro-EMT effect of HMGA2 in vitro and in vivo. Therefore, our data reveal that HMGA2 promotes IUA formation and suggest that let-7d can depress HMGA2 and may be a clinical targeting strategy in IUA.

Automated summary

This study demonstrates the overexpression of HMGA2 in endometrial epithelial cells of intrauterine adhesion patients, promoting the formation of intrauterine adhesions. It also suggests that let-7d microRNA can suppress the effects of HMGA2, potentially serving as a therapeutic strategy for intrauterine adhesions.