MicroRNA 449c Mediates the Generation of Monocytic Myeloid-Derived Suppressor Cells by Targeting STAT6

Myeloid-derived suppressor cells (MDSCs) promote tumour progression by contributing to angiogenesis, immunosuppression, and immunotherapy resistance. Although recent studies have shown that microRNAs (miRNAs) can promote the expansion of MDSCs in the tumour environment, the mechanisms involved in this process are largely unknown. Here, we report that microRNA 449c (miR-449c) expression was upregulated in myeloid progenitor cells upon activation of C-X-C motif chemokine receptor 2 (CXCR2) under tumour conditions. MiR-449c upregulation increased the generation of monocytic MDSCs (mo-MDSCs). The increased expression of miR-449c could target STAT6 mRNA in myeloid progenitor cells to shift the differentiation balance of myeloid progenitor cells and lead to an enhancement of the mo-MDSCs population in the tumour environment. Thus, our results demonstrate that the miR-449c/STAT6 axis is involved in the expansion of mo-MDSCs from myeloid progenitor cells upon activation of CXCR2, and thus, inhibition of miR-449c/STAT6 signalling may help to attenuate tumour progression.