Tumor suppressive role of microRNA-139-5p in bone marrow mesenchymal stem cells-derived extracellular vesicles in bladder cancer through regulation of the KIF3A/p21 axis

The emerging roles of extracellular vesicles (EVs) in bladder cancer have recently been identified. This study aims to elucidate the role of microRNA-139-5p (miR-139-5p) shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived EVs (BMSCs-EVs) in bladder cancer, with the possible mechanism explored. Expression of miR-139-5p and KIF3A was tested, followed by an analysis of their correlation. EVs were isolated from BMSCs and co-cultured with T24 or BOY-12E cells with miR-139-5p mimic/inhibitor, oe-KIF3A, and/or si-p21 transfected to study the roles of miR-139-5p/KIF3A/p21 in bladder cancer cell functions. A nude mouse model of subcutaneous xenograft tumor was constructed to detect the effect of miR-139-5p in BMSCs-EVs on the tumorigenesis and lung metastasis of bladder cancer cells in vivo. It was identified that miR-139-5p was highly expressed in BMSCs-EVs, but poorly expressed in bladder cancer. BMSCs-EVs transferred miR-139-5p into bladder cancer cells where miR-139-5p inhibited the malignant features of bladder cancer cells in vitro. miR-139-5p in BMSCs-EVs targeted KIF3A and inhibited the expression of KIF3A, thereby activating p21. miR-139-5p in BMSCs-EVs arrested the tumorigenesis and lung metastasis of bladder cancer cells in vivo by modulation of the KIF3A/p21 axis. Altogether, BMSCs-EVs carried miR-139-5p targeted KIF3A to activate p21, thus delaying the occurrence of bladder cancer.