MicroRNA-320a-containing exosomes from human umbilical cord mesenchymal stem cells curtail proliferation and metastasis in lung cancer by binding to SOX4.

ABSTRACT

Exosomes from human umbilical cord mesenchymal stem cells (HUCMSCs) containing microRNAs (miRNAs) have been underscored as possible therapeutic options for cancers. Hence, our goal here was to investigate the relevance of miR-320a-containing exosomes from HUCMSCs to lung cancer. First, H1299 and H460 cells were co-cultured with the exosomes overexpressing miR-320a from HUCMSCs. The data displayed that HUCMSCs-secreted exosomes expressing miR-320a exerted anti-tumor effects in vitro and in vivo. Online analysis available at TargetScan database revealed that miR-320a bound to sex-determining region Y-box 4 (SOX4), and the luciferase reporter gene assay clarified this targeting relationship. Next, a ß-catenin-specific agonist WAY-262611 was delivered into the H1299 and H460 cells to assess the effects of the Wnt/ß-catenin pathway on lung cancer cellular processes. The results demonstrated that WAY-262611 potentiated lung cancer cell viability, invasion, and migration, but inhibited cell apoptosis. Altogether, exosomes carrying miR-320a from HUCMSCs might suppress lung cancer cell growth via the SOX4/Wnt/ß-catenin axis, which highpoints the potency of exosomes expressing miR-320a as a possible therapeutic option for lung cancer treatment.