Exosomal circPVT1 derived from lung cancer promotes the progression of lung cancer by targeting miR-124-3p/EZH2 axis and regulating macrophage polarization

Abstract

ABSTRACT This study aims to probe the mechanism by which circPVT1 in lung cancer (LC)-derived exosomes (Exos) promotes proliferation, invasion and migration of LC cells by regulating macrophage polarization through miR-124-3p/EZH2 axis. The expressions of circPVT1 in blood-derived Exos extracted from lung adenocarcinoma (LA) patients were measured. Loss or gain-of-function experiments of circPVT1 and miR-124-3p were carried out to evaluate the effects of circPVT1 in LC-derived Exos and miR-124-3p on macrophage polarization toward M2 phenotype, whichi found that incubation of Exo-A with macrophages induced macrophage polarization to M2 type and M2-polarized macrophages co-incubated with A549 cells enhanced the biological function of LC cells. Co-incubation with M+ Exo-A-oecircPVT1 increased the proliferation, migration and invasion abilities of LC cells, while coculture with M+ Exo-A-si-circPVT1 reversed these abilities. The verification among circPVT1, miR-124-3p and EZH2 showed that miR-124-3p was negatively related to circPVT1 and EZH2, and EZH2 was positively related to circPVT1. CircPVT1 in LC-derived Exos increased EZH2 expression through inhibiting miR-124-3p expression level in macrophage. Taken togther, exosomal circPVT1 derived from LC mediates macrophage polarization via the miR-124-3p/EZH2 axis to potentiate LC cells’ proliferation, invasion and migration.