MicroRNA-21 Derived from Exosomes of Bone Marrow Mesenchymal Stem Cells (BMSCs) Alleviates Pancreatic Cancer by Downregulation of a Disintegrin and Metalloprotease 9 (ADAM9)
We aimed to explore underlying mechanism by which microRNA-21 (miR-21) derived from bone marrow mesenchymal stem cells (BMSCs) extracted exosomes (exo) in pancreatic cancer (PC). Bioinformatics analysis identified candidate miRNAs and target mRNAs in PC those were verified by luciferase reporter assay. BMSCs and exo were isolated and co-cultivated with PC cells. PC cells were then treated with plasmids loaded with miR-21 or a disintegrin and metalloprotease 9 (ADAM9), followed by detection of invasion, metastasis and apoptosis through Transwell assay and flow cytometry. MiR-21 was downregulated in PC tissues and cells, while ADAM9 was upregulated and positively correlated with poor prognosis. Overexpression of miR-21 restrained the capacities of proliferation, invasion and migration of PC cells by inhibiting ADAM9 expression. Specific inhibitor GW4869 reduced release of exo and declined miR-21 expression. Treatment with BMSC-exo containing miR-21 suppressed the malignant characteristics of cancer cells. MiR-21 derived from exo of BMSCs inhibited PC progression by ADAM9 down-regulation, providing insight into novel strategy against PC.