Diagnostic and mechanistic roles of miR-5584-5p in endometriosis via the FZD2-mediated Wnt/β-catenin EMT axis

Abstract

The early detection of endometriosis (EM), a significant cause of dysmenorrhea, is essential for effective clinical management. This study sought to determine the functional role of miR-5584-5p in EM and the mechanistic involvement of its target, FZD2, in disease progression. This case-control study enrolled 217 dysmenorrhea patients (107 EM cases and 110 controls). Ishikawa cells with modulated miR-5584-5p and FZD2 expression were used to assess cell proliferation, migration, and invasion. The miR-5584-5p/FZD2 interaction and Wnt/β-catenin transcriptional activity were validated by dual-luciferase and TOP/FOP flash reporter assays. Serum miR-5584-5p was significantly downregulated in EM patients, demonstrating high diagnostic accuracy (AUC = 0.903) and acting as an independent protective factor. In vitro, miR-5584-5p overexpression suppressed Ishikawa cell proliferation, migration, and invasion, concurrently inhibiting Wnt/β-catenin transcriptional activity and the epithelial-mesenchymal transition (EMT) axis. FZD2 was confirmed as a direct target of miR-5584-5p. Crucially, FZD2 overexpression partially reversed the inhibitory effects of miR-5584-5p on malignant cellular phenotypes and restored Wnt/β-catenin signaling. Serum miR-5584-5p serves as a valuable potential diagnostic biomarker for EM. Functionally, it attenuates endometrial epithelial cell aggressiveness by targeting FZD2 and suppressing the Wnt/β-catenin-EMT axis. Future studies utilizing primary cells and in vivo models are warranted to validate these preliminary mechanisms.