Abstract
Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set 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 quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-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 on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3+ T cell proliferation and the proportion of interferon (IFN)-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate 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.
Highlights
Colon cancer is the third leading cause of cancer-related deaths across the world, with a measly survival rate of 10% if diagnosed at late stage.[1]
The isolated M2 macrophages were cocultured with SW48 colon cancer cells, in order to investigate whether M2 macrophages affected colon cancer progression
The results (Figures 1C and 1D) showed that compared with SW48 cells cocultured with M1 macrophages or phosphate-buffered saline (PBS), those cocultured with M2 macrophages presented with increased proliferation and antiapoptotic abilities, indicating that M2 macrophages were positively correlated with colon cancer development
Summary
Colon cancer is the third leading cause of cancer-related deaths across the world, with a measly survival rate of 10% if diagnosed at late stage.[1]. Metastasis is the leading cause of death in patients with late-stage colon cancer.[5,6] On the other hand, the process of immune escape is significantly relevant to tumor survival; investigating its mechanisms could aid the development of newer and more effective therapeutic options for colon cancer.[7,8]
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