Oestrogen induces epithelial-mesenchymal transition in endometriosis via circ_0004712/miR-148a-3p sponge function.

Endometriosis is a common, chronic gynaecologic disease affecting up to 10% of women in their reproductive age and leading to pain and infertility. Oestrogen (E2 )-induced epithelial-mesenchymal transition (EMT) process has been considered as a key factor of endometriosis development. Recently, the dysregulated circular RNAs (circRNAs) have been discovered in endometriosis tissues. However, the molecular mechanism of circRNAs on the E2 -induced EMT process in endometriosis is still unknown. Here, we demonstrated that circ_0004712 up-regulated by E2 treatment in endometrial epithelial cells. Knock-down the expression of circ_0004712 significantly suppressed E2 -induced cell migration activity. Meanwhile, we identified miR-148a-3p as a potential target miRNA of circ_0004712. Inhibited the expression of miR-148a-3p could recovered the effect of circ_0004712 knock-down in E2 -treated endometrial epithelial. Furthermore, Western blot assay showed that E2 treatment could increase the expression and activity of ß-catenin, snail and N-cadherin and reduce the expression of E-cadherin. The expression and activity of ß-catenin pathway were recovered by circ_0004712 knock-down or miR-148a-3p overexpression. Altogether, the results demonstrate that circ_0004712/miR-148a-3p plays an important role in E2 -induced EMT process in the development of endometriosis, and the molecular mechanism may be associated with the ß-catenin pathway. This work highlighted the importance of circRNAs in the development of endometriosis and provide a new biomarker for diagnosis and therapies.