Exosomal miR-22-3p derived from peritoneal macrophages enhances proliferation, migration, and invasion of ectopic endometrial stromal cells through regulation of the SIRT1/NF-κB signaling pathway

L. Zhang, H.-H. Li, M. Yuan, D. Li, G.-Y. Wang

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China. wangguoy@sdu.edu.cn

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• Gynecology

OBJECTIVE: Exosomes play crucial roles in cell-cell communication, but few studies exist on the role of exosomal miRNA in the interaction between peritoneal macrophages (pMφ) and human ectopic endometrial stromal cells (eESCs) in endometriosis (EMS). This study aimed to identify which exosomal miRNAs are significantly differently produced from EMS pMφ and to investigate the functional role of exosomal miRNAs in eESCs.

PATIENTS AND METHODS: Exosomes were collected from the culture media of pMφ by differential centrifugation. Confocal microscopy was used to identify whether the exosomes secreted by pMφ can be delivered into eESCs. miRNA microarray and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) were used to identify which exosomal miRNAs were specifically elevated in pMφ-derived exosomes from EMS and delivered into eESCs via exosomes. The effect of pMφ-derived miR-22-3p on the biological function of eESCs was assessed by Cell Counting Kit-8 (CCK-8), wound-healing, and transwell chamber assays. Bioinformatics analysis and Luciferase reporter assay were used to detect the binding of exosomal miR-22-3p to the 3′untranslated region of SIRT1. Western blot was utilized to detect the activity of SIRT1/NF-κB pathway.

RESULTS: Exosomes secreted by pMφ can successfully be transported to eESCs. pMφ-derived exosomes from EMS promoted the proliferation, migration, and invasion of eESCs. MiR-22-3p was significantly increased in pMφ-derived exosomes from EMS and delivered from pMφ to eESCs via exosomes. Mechanistic analyses revealed that exosomal miR-22-3p from pMφ promoted the proliferation, migration, and invasion of eESCs by targeting SIRT1 and activating NF-κB pathway.

CONCLUSIONS: Exosomal miR-22-3p promotes the proliferation, migration, and invasion of eESCs by regulating SIRT1/NF-κB pathway and may serve as a novel target for the inhibition of EMS progression.

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