miR-223 suppresses differentiation of tumor-induced CD11b+Gr1+myeloid-derived suppressor cells from bone marrow cells
✍ Scribed by Qiaofei Liu; Miaomiao Zhang; Xingran Jiang; Zhiqian Zhang; Lingyun Dai; Siping Min; Xilong Wu; Qingsheng He; Jingyi Liu; Yuan Zhang; Zhujun Zhang; Rongcun Yang
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- French
- Weight
- 856 KB
- Volume
- 129
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Tumor‐associated factors are related to increased accumulation of CD11b^+^Gr1^+^myeloid‐derived suppressor cells (MDSCs). However, the exact mechanism of how genetic factors control the expansion of MDSCs in tumor‐bearing hosts remains elusive. Herein, we found that tumor‐associated MDSCs and their subsets, mononuclear MDSCs and polymorphonuclear MDSCs, have decreased expression of miR‐223 when compared to CD11b^+^Gr1^+^ cells from the spleen of disease‐free mice. With the differentiation of CD11b^+^Gr1^+^MDSCs from bone marrow cells (BMCs) upon exposure to tumor‐associated factors, the expression of both pri‐miR‐223 and mature miR‐223 was downregulated, indicating that the expression of miR‐223 could be regulated by tumor‐associated factors. Interestingly, miR‐223 remarkably inhibits differentiation of BMCs into CD11b^+^Gr1^+^MDSCs in the presence of tumor‐associated factors by targeting myocyte enhancer factor 2C (MEF2C). Using reconstituted s.c. tumor models, miR‐223 also suppresses accumulation of CD11b^+^Gr1^+^MDSCs, whereas its targeting molecule MEF2C increases the number of MDSCs. Tumor growth is slower in mice infused by miR223‐engineered BMCs than in mice infused with control transfected BMCs. As miR‐223 and its target molecule MEF2C are highly conserved between mice and humans, the modulation of miR‐223 in tumor‐induced CD11b^+^Gr1^+^MDSCs may exert an important role in controlling the increased accumulation of CD11b^+^Gr1^+^MDSCs in patients with tumor.