miR‐34a inhibits the apoptosis of MDSCs by suppressing the expression of N‐myc

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors, which possess strong immunosuppressive functions. MDSCs are found in increased numbers in infectious and inflammatory pathological conditions. However, whether microRNAs have a role in the expansion remains unclear. Here in our study, we found that overexpression of miR-34a could induce the expansion of MDSCs in the bone marrow and spleen both in chimera and transgenic mice. And further experiments demonstrated that miR-34a inhibited the apoptosis through reduced translation of N-myc without affecting the proliferation. Luciferase assay and western blotting experiments implied that N-myc is the direct target of miR-34a in MDSCs. Overexpressed mir-34a changes the cytokine expression profile in MDSCs and skewed the MDSCs to M1 phenotype. And miR-34a-overexpressed MDSCs significantly slowed down the tumor growth. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis via suppressing the expression of N-myc.