M1 Macrophage-Derived Exosomal MicroRNA-326 Suppresses Hepatocellular Carcinoma Cell Progression Via Mediating NF-κB Signaling Pathway

Abstract

AbstractAccumulating evidence has shown that microRNA (miR) derived from M1 macrophage-derived exosomes can regulate the progression of hepatocellular carcinoma (HCC). However, the effect of miR-326 derived from M1 macrophage-derived exosomes on HCC has not been reported. Therefore, the objective of the present study was to explore the mechanism of exosomal miR-326 from M1 macrophages in regulating HCC cell progression. RT-qPCR detected miR-326 expression in HCC cell lines. miR-326 expression in HCC was altered by transfection, and the effect of miR-326 on CD206 and NF-κB expression, cell proliferation, colony formation, migration, apoptosis and invasion was detected. Subsequently, exosomes were isolated from M1 macrophages. RT-qPCR identified miR-326 expression in M1 macrophage-derived exosomes. miR-326 expression in M1 macrophage-derived exosomes was changed by transfection. M1 macrophage-derived exosomes were co-cultured with HCC cells to figure out their effects on the biological progress of HCC cells. Finally, in vivo experiments were performed to verify the in vitro results. MiR-326 was decreased in HCC cells and enriched in M1 macrophage-derived exosomes. Up-regulating miR-326 would inhibit HCC cell proliferation, colony formation, migration, invasion, and CD206 and NF-κB expression and promoted apoptosis, and inhibited the growth of HCC tumors in vivo, while down-regulating miR-326 showed opposite effects. M1 macrophage-derived exosomes inhibited HCC cell proliferation, colony formation, migration, invasion, and CD206 and NF-κB expression and enhanced apoptosis, while overexpression of miR-326 enhanced the effect of M1 macrophage-derived exosomes on HCC cells. It is revealed that M1 macrophages-derived exosomal miR-326 suppresses proliferation, migration and invasion as well as advances apoptosis of HCC through down-regulating NF-κB expression.