Mesenchymal stem cell-derived exosomes carrying microRNA-150 suppresses the proliferation and migration of osteosarcoma cells via targeting IGF2BP1

Abstract

Background

MicroRNA-150 (miR-150) plays a critical role in varied types of human cancers. In this study, we explored the effect and mechanism of mesenchymal stem cell (MSC)-derived exosomes (exo) carrying miR-150 (MSC-Exo-150) on the proliferation, migration, invasion, and apoptosis of osteosarcoma (OS) cells.

Methods

MiR-150 expression in OS cell lines was assessed by quantitative reverse-transcription PCR (qRT-PCR). MSCs were transfected with cell-miR-67 or has-miR-150, and grouped as MSC-67 or MSC-150. Exosomes were isolated from each group, and separately named MSC-Exo-67, MSC-Exo-150 and MSC-Exo. MTT or flow cytometry assay was used to analyze the proliferation or apoptosis of U2SO and HOS cells, respectively. Wound healing or transwell assay was utilized to examine the migration or invasion of U2SO and HOS cells, respectively. The target relationship of miR-150 and insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) was established using StarBase2.0 and verified by dual-luciferase reporter gene analysis. Xenografted tumor model was established in rats to confirm the inhibitory effect of MSC-Exo-150 on the growth of xenografted tumor in vivo.

Results

The expression of miR-150 was downregulated in OS cell lines, and significantly higher in MSC-150 cells than that in MSCs. MiR-150 was overexpressed in MSC-Exo-150 group compared with MSC-Exo group. After transfection of MSC-Exo-150 into U2SO and HOS cells, cell viability, mobility and invasion rate were decreased, and the cell apoptosis was increased. MiR-150 targeted IGF2BP1 and IGF2BP1 expression was negatively modulated by miR-150. Overexpression of IGF2BP1 reversed the anti-tumor effect of MSC-Exo-150 on HOS cells.

Conclusions

MSC-Exo-150 inhibited proliferation, migration, invasion, and induced apoptosis of OS cells by targeting IGF2BP1.