MicroRNAs associated with adenomyosis promote endometrial epithelial cell migration via MMP-2 and MMP-9 upregulation†

Adenomyosis is a common gynecological disorder characterized by the presence of endometrial tissue in the myometrium, causing chronic pelvic pain and abnormal bleeding. Although dysregulated microRNAs (miRNAs) in stromal cells of adenomyosis patients have been implicated in disease-associated extracellular matrix (ECM) remodeling, their role in regulating endometrial epithelial cell (EEC) behavior remains poorly understood. This study investigated the effect of selected adenomyosis- and endometriosis-associated miRNAs on EEC migration and matrix metalloproteinase (MMP) expression. Ishikawa cells, a human endometrial epithelium-like cell line, were transfected with mimics and inhibitors of Let-7b, miR-451a, miR-125b, miR-7 and miR-150. Cell migration was assessed using wound healing assays. MMP-2 and MMP-9 mRNA expression were quantified by quantitative real-time polymerase chain reaction, while protein production and secretion were evaluated by enzyme-linked immunosorbent assay. Transfection with Let-7b-5p inhibitor and miR-451a, miR-125b-1 and miR-150 mimics significantly enhanced cell migration and led to increased MMP-2 and MMP-9 mRNA expression, intracellular protein levels and secretion. These findings suggest that these miRNAs promote EEC migration and ECM remodeling through MMP upregulation, pointing to a potential mechanism for lesion formation in adenomyosis. Future research should seek to validate these findings in primary EECs and explore the therapeutic potential of targeting miRNA-MMP pathways for adenomyosis treatment.