ABSTRACT
Objective · To determine the expression of miRNA-7 in TWEAK-stimulated macrophages and their secreted exosomes;to investigate the role of exosomal miRNA-7 from TWEAK-stimulated macrophages in modulating the metastasis of epithelial ovarian cancer (EOC) cells.Methods · Real-time PCR analysis was used to determine the miRNA-7 expression in TWEAK-stimulated macrophages,their exosomes and recipient HO8910-PM cells.The activity of EGFR signaling pathway in HO8910-PM cells was detected by Western blotting analysis.AntagomiR-7 was used to downregulate the miRNA-7expressions in macrophage exosomes and then their effect on metastasis of HO8910-PM cells was examined by transwell assay.Results ·TWEAK increased the levels of miRNA-7 in macrophages and their secreted exosomes and also resulted in an elevated level of miRNA-7 in recipient HO8910-PM cells,which eventually reduced the activity of EGFR/AKT/ERK1/2 pathway.Pre-transfection of antagomiR-7 remarkably decreased the levels of miRNA-7 in macrophages,their secreted exosomes and the recipient EOC cells,with the enhancement of HO8910-PM metastasis.Conclusion · Exosomal miRNA-7 from TWEAK-stimulated macrophages plays a critical role in suppressing the metastasis of EOC cells by attenuation of EGFR signaling pathway.