MiR-518c-3p alleviates endometriosis by inhibiting ectopic endometrial migration and epithelial-mesenchymal transition via targeting ZNF608

Purpose The present study was performed to clarify the regulatory mechanism of miR-518c-3p in the progression of endometriosis (EMs). Methods MicroRNAs (miRNAs) potentially acting on EMs were predicted by bioinformatics databases and validated in normal and ectopic endometrium. The miR-518c-3p mimics were transfected into endometrial stromal cells (ESCs), and cell growth, death, and proliferation marker proteins expression were detected. The targeting relationship of miR-518c-3p with zinc finger protein 608 (ZNF608) was validated by luciferase reporter assay. ESCs were incubated with miR-518c-3p mimics alone or co-transfected with pcDNA-ZNF608, and growth, death, as well as proliferation and epithelial-mesenchymal transition (EMT) marker protein expression were detected. A rat model of EMs overexpressing miR-518c-3p alone or ZNF608 simultaneously was constructed to detect ectopic endometrial cell apoptosis and cyst volume in rats. Results MiR-518c-3p expression was downregulated in ectopic endometrium. MiR-518c-3p mimic inhibited migration, invasion and proliferation of ESCs, and promoted apoptosis. MiR-518c-3p targeted the 3'UTR of ZNF608. ZNF608 expression was upregulated in ESCs and ectopic endometrium, and the regulatory effect of pcDNA-ZNF608 on ESCs was opposite to that of miR-518c-3p mimics. ZNF608 overexpressing rats had greater endometrial cyst weight and volume, and decreased endometrial apoptosis compared with miR-518c-3p overexpressing alone. Conclusion MiR-518c-3p inhibited growth, metastasis and EMT of ESCs and decreased ectopic endometrial area in rats with EMs by targeting ZNF608.

Automated summary

The study aimed to clarify the regulatory mechanism of miR-518c-3p in the progression of endometriosis. The results demonstrated that miR-518c-3p inhibits the growth, metastasis, and EMT of ESCs by targeting ZNF608, thereby reducing the ectopic endometrial area in rats with EMs.