MicroRNA-9 modulates the maturation and function of myeloid-derived suppressor cells by targeting Runx1 (TUM4P.902)

Abstract Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression, which hampers effective immunotherapeutic approaches. Our previous study showed that β-glucans could differentiate monocytic MDSCs (M-MDSCs) into mature myeloid cells and impair the suppressive function of MDSCs. However, the molecular networks are largely unknown. MicroRNAs (miRNAs) are involved in the regulation of immunity, including the immune cell development and differentiation. In this study, we identified that the expression of microRNA-9 (miR-9) was dramatically reduced after β-glucan stimulation, which was considered an essential player in modulating the maturation and function of MDSCs. Overexpressing miR-9 could significantly enhance the activity of MDSCs and reverse β-glucan induced maturation by targeting runt related transcription factor 1 (Runx1) while down-regulating miR-9 remarkably enhanced the maturation of MDSCs and impaired the suppressive effect of the cells. In addition, down-regulation of Runx1 resulted in increased suppressive effect of MDSCs and inhibited the maturation process. Furthermore, knockdown of miR-9 significantly impaired the activity of MDSCs and inhibited the tumor growth in vivo. Collectively, our findings reveal that miR-9 expression in MDSCs plays a critical role in the molecular events governing the maturation and function of MDSCs and might be identified as a potential target in cancer therapy.