Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

Abstract

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetantroles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehiclesto deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitorsignificantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an oppositeeffect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventionaltransfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reducedapoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoterby targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficientinhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could beuseful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understandingof the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.