MicroRNA-488 inhibits endometrial glandular epithelial cell proliferation, migration, and invasion in endometriosis mice via Wnt by inhibiting FZD7

Endometriosis is a chronic inflammatory syndrome and nearly 6%40% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR-488 would effectively inhibit the development of endometriosis. The microarray-based data analysis was performed to screen endometriosis-related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR-488 in mice with endometriosis, we measured miR-488 expression and expression levels of Frizzled-7 (FZD7), cyclinD1, beta-catenin, and c-Myc in vivo and in vitro. Finally, we detected the effect of miR-488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, beta-catenin, c-Myc and cyclinD1, and lower miR-488 expression in mouse endometrial tissues. FZD7 was the target gene of miR-488. Furthermore, elevated miR-488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of beta-catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up-regulated miR-488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down-regulating FZD7.