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

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Jul 12

PMID 35821021

Authors

Ying Xiang

Dong Lv

Tao Song

Chao Niu

Ying Wang

Affiliations

Soon will be listed here.

Abstract

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.

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