期刊
INTERNATIONAL JOURNAL OF CANCER
卷 129, 期 11, 页码 2662-2673出版社
WILEY
DOI: 10.1002/ijc.25921
关键词
myeloid-derived suppressor cells; miR-223; MEF2C
类别
资金
- NSFC [30771967, 30872315]
- Ministry of Science and Technology [2008AA02Z129]
- National Key Basic Research and Development Program of China (973 Program) [2007CB914803]
- National Key Scientific Program [2011CB964902]
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.
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