M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B

Abstract Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRs). The current study sets out to explore the possible role of M2 macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from RT-qPCR and Western blot analysis revealed highly-expressed miR-155-5p and IL-6, and poorly-expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophages-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3’-UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation of miR-155-5p and ZC3H12B in the SW48 and HT29 cells co-cultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p over-expression or ZC3H12B silencing promoted the proliferation and anti-apoptosis ability of SW48 and HT29 cells, as well as augmented the CD3+ T cell proliferation and the proportion of IFN-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to up-regulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.