Mesenchymal stem cell-derived extracellular vesicles transfer miR-598 to inhibit the growth and metastasis of non-small-cell lung cancer by targeting THBS2

Abstract

AbstractNon-small-cell lung cancer (NSCLC) is the subtype of lung cancer, which accounts for about 85% of diagnosed lung cancer cases, and is without any effective therapy. Emerging evidence has revealed microRNA-598 (miR-598) as potential therapeutic target and diagnostic marker of NSCLC. In the present study, we sought to define the role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing miR-598 in NSCLC. Co-culture experiments were conducted to examine the secretion of miR-598 by MSCs and the uptake of EVs by NSCLC cells. The expression of miR-598 in NSCLC cell lines, tissues, and MSC-derived EVs was detected by the RT-qPCR. After treatment with MSCs-EVs, CCK-8 and Transwell assays were adopted to evaluate the effects of miR-598 on proliferation, migration, and invasion capacities of NSCLC cells. Finally, the effects of miR-598 on tumor growth and metastasis were further validated in vivo through subcutaneous tumorigenesis and experimental pulmonary metastasis in nude mice. We found that MSCs-derived EVs could deliver miR-598 into NSCLC cells, where miR-598 specifically targeted and bound with mRNA of THBS2 to inhibit its translational process. By suppressing the promoting effects of THBS2 on the proliferation, migration, and invasion of NSCLC cells, the EV treatment reduced the progression of NSCLC. Notably, these inhibitory effects were reversed by concomitantly overexpressing THBS2. Overall, we find that MSCs-derived EVs containing miR-598 targets THBS2 to inhibit the proliferation and migration of NSCLC cells in vivo and in vitro.