The Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, Changchun 130024, China.
Mol Cells. 2020 Sep 30;43(9):793-803. doi: 10.14348/molcells.2020.2307.
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.
髓系来源的抑制性细胞 (MDSCs) 通过促进血管生成、免疫抑制和免疫治疗耐药来促进肿瘤进展。尽管最近的研究表明 microRNAs (miRNAs) 可以促进肿瘤微环境中 MDSCs 的扩增，但这一过程涉及的机制在很大程度上尚不清楚。在这里，我们报告说，在肿瘤条件下，C-X-C 基序趋化因子受体 2 (CXCR2) 激活后，髓系祖细胞中的 microRNA 449c (miR-449c) 表达上调。miR-449c 的上调增加了单核细胞 MDSCs (mo-MDSCs) 的产生。miR-449c 的高表达可以靶向髓系祖细胞中的 STAT6 mRNA，从而改变髓系祖细胞的分化平衡，并导致肿瘤微环境中 mo-MDSCs 群体的增强。因此，我们的结果表明，在 CXCR2 激活时，miR-449c/STAT6 轴参与了 mo-MDSCs 从髓系祖细胞的扩增，因此，抑制 miR-449c/STAT6 信号通路可能有助于减弱肿瘤进展。
