Exosomal miR-22-3p targets p53 to regulate endometrial epithelial cell function in the pathogenesis of endometriosis

Abstract

Endometriosis (EMs) is a widespread gynecological disease, affecting approximately 6-10% of females of child-bearing age. Despite its significant influence on women's health, the specific pathophysiology remains unclear. The enrichment of miR-22-3p in exosomes has been implicated in cellular proliferation and migration. This study aimed to elucidate the mechanisms by which exosomal miR-22-3p affects endometrial epithelial cell function in the etiology of endometriosis. The patient samples and clinical data were acquired from the Affiliate Hospital of Inner Mongolia Medical University. Quantitative reverse transcription‒polymerase chain reaction (qRT‒PCR), a miRNA microarray and Western blotting were used to confirm that the level of miR-22-3p was specifically elevated in peripheral blood exosomes from EMs patients. The influence of miR-22-3p on EMs-derived exosomes was determined by Transwell and cell counting kit-8 (CCK-8) assays. Luciferase reporter assays, RNA pull-down assays, and fluorescence in situ hybridization (FISH) were performed to determine whether exosomal miR-22-3p binds to p53. miR-22-3p expression was significantly elevated in peripheral blood exosomes (p < 0.001) from patients with endometriosis. ROC curve analysis demonstrated the high sensitivity (93.55%) and specificity (84.85%) of this correlation, suggesting that miR-22-3p is a promising diagnostic biomarker. Endometrial epithelial cell proliferation, migration, and invasion are regulated by exosomal miR-22-3p, which targets and inhibits p53, a crucial tumor suppressor related to cell cycle regulation and apoptosis. Exosomal miR-22-3p regulates endometrial epithelial cell proliferation, migration, and invasion by targeting and inhibiting p53. Combining standard endometriosis treatments with exosome-mediated miR-22-3p targeting of p53 could restore p53 function, induce apoptosis, and reduce disease recurrence, providing a promising therapeutic strategy for endometriosis management.