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).

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.

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.

MiR-518c-3p inhibited growth, metastasis and EMT of ESCs and decreased ectopic endometrial area in rats with EMs by targeting ZNF608. Similar content being viewed by others Availability of data and materials All data generated or analyzed during this study are included in this published article.

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We sincerely appreciate the supports of all participants. Funding This work was supported by the Wannan Medical College Natural Science Research Project (JXYY202147). Author information Authors and Affiliations Contributions BL and FX conceived and designed the study. BL and XC analyzed the data. YY and ST conducted most of the experiments and performed the literature search and data extraction. BL drafted the manuscript. XC and FX finalized the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Conflict of interest The authors state that there are no conflicts of interest. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Ethics approval and consent to participate The analysis was performed according to the principles of the Helsinki Declaration. Written informed consent was obtained from all patients. The experimental protocol was approved by the Ethics Committee of First Affiliated Hospital of Soochow University. Consent for publication The authors give consent to the publication in the journal. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Lu, B., Cao, X., chen, X. et al. MiR-518c-3p alleviates endometriosis by inhibiting ectopic endometrial migration and epithelial–mesenchymal transition via targeting ZNF608. Arch Gynecol Obstet 307, 205–213 (2023). https://doi.org/10.1007/s00404-022-06439-x Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-022-06439-x