Engineered exosomes restore miR-508-5p expression in uterine corpus endometrial carcinoma and reduce tumor progression and metastasis by targeting DLL3

Introduction Endometrial cancer (EC) is a growing global health concern. Understanding the molecular mechanisms driving EC is crucial for developing effective diagnostic and therapeutic strategies. This study investigates the roles of DLL3 and miR-508-5p in EC progression and explores a therapeutic approach using engineered exosomes to modulate their expression. Methods TCGA data were analyzed, in vitro and in vivo experiments were performed to assess DLL3 and miR-508-5p function, and bioinformatics was used to confirm their interaction. Mesenchymal stem cells (MSCs) were engineered to produce miR-508-5p-overexpressing exosomes, and their therapeutic effects were tested in mouse models. Results Elevated DLL3 and downregulated miR-508-5p were observed in EC and correlated with poor outcomes. miR-508-5p directly targets DLL3. Engineered exosomes restored miR-508-5p, inhibited DLL3, and reduced tumor growth and metastasis in mouse models. Discussion The findings highlight the roles of DLL3 and miR-508-5p in EC. Targeting the miR-508-5p/DLL3 axis via exosome-mediated delivery represents a promising therapeutic strategy for EC.