Bone Marrow Mesenchymal Stem Cells-Derived Exosomal microRNA-19b-1-5p Reduces Proliferation and Raises Apoptosis of Bladder Cancer Cells Via Targeting ABL2

Abstract

Background: In recent years, accumulating evidence has demonstrated the role of microRNAs (miRs) in bladder cancer, however, the mechanisms underlying miR-19b-1-5p in bladder cancer remain largely unknown, thus, we aim to investigate the effect of exosomal miR-19b-1-5p targeted non-receptor protein tyrosine kinase Arg (also called ABL2) on biological characteristics of bladder cancer cells.

Methods: miR-19b-1-5p and ABL2 expression was tested in bladder cancer tissues and cells. We then conducted miR-19b-1-5p inhibition/overexpression assays to determine bladder cancer cell invasion, proliferation, migration and apoptosis. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). BMSC-exosomes (Exo) and T24 cells were co-cultured to verify the function of Exo-miR-19b-1-5p mimic in biological characteristics of bladder cancer cells. Finally, the effects of Exo-miR-19b-1-5p and depleted ABL2 were investigated in vivo by measuring tumor formation in nude mice.

Results: miR-19b-1-5p expression was decreased while ABL2 expression was increased in bladder cancer tissues and cells. Up-regulated miR-19b-1-5p and Exo-miR-19b-1-5p mimic suppressed invasion, proliferation and migration ability as well as facilitated apoptosis of bladder cancer cells. Down-regulated miR-19b-1-5p and combination of up-regulated miR-19b-1-5p and ABL2 presented an opposite result. Up-regulated Exo-miR-19b-1-5p or depleted ABL2 declined the volume and weight of tumor in nude mice.

Conclusion: Our study proved that BMSCs-derived exosomal miR-19b-1-5p suppresses invasion, proliferation and migration while facilitates apoptosis of bladder cancer cells through down-regulation of ABL2. Thus, miR-19b-1-5p may be a potential candidate for treatment of bladder cancer.

Funding Statement: The work was funded by National Natural Science Foundation of China (Grant number:NSFC81672265).

Declaration of Interests: The authors declare that they have no conflicts of interest.

Ethics Approval Statement: This study was approved and supervised by the Animal Ethics Committee of The First Affiliate Hospital of Jinzhou Medical University. The treatment of animals in all experiments conforms to the ethical standards of experimental animals.