PMID- 21213211 OWN - NLM STAT- MEDLINE DCOM- 20111129 LR - 20171116 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 129 IP - 11 DP - 2011 Dec 1 TI - miR-223 suppresses differentiation of tumor-induced CD11b(+) Gr1(+) myeloid-derived suppressor cells from bone marrow cells. PG - 2662-73 LID - 10.1002/ijc.25921 [doi] AB - 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. CI - Copyright (c) 2011 UICC. FAU - Liu, Qiaofei AU - Liu Q AD - Key Laboratory of Bioactive Materials, Department of Immunology, Ministry of Education, Nankai University School of Medicine, Nankai University, Tianjin, China. FAU - Zhang, Miaomiao AU - Zhang M FAU - Jiang, Xingran AU - Jiang X FAU - Zhang, Zhiqian AU - Zhang Z FAU - Dai, Lingyun AU - Dai L FAU - Min, Siping AU - Min S FAU - Wu, Xilong AU - Wu X FAU - He, Qingsheng AU - He Q FAU - Liu, Jingyi AU - Liu J FAU - Zhang, Yuan AU - Zhang Y FAU - Zhang, Zhujun AU - Zhang Z FAU - Yang, Rongcun AU - Yang R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110325 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (CD11b Antigen) RN - 0 (Gr-1 protein, mouse) RN - 0 (MEF2 Transcription Factors) RN - 0 (MIRN223 microRNA, mouse) RN - 0 (Mef2c protein, mouse) RN - 0 (MicroRNAs) RN - 0 (Myogenic Regulatory Factors) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Chemokine) SB - IM MH - Animals MH - Blotting, Western MH - Bone Marrow Cells/*immunology MH - CD11b Antigen/*metabolism MH - Cell Differentiation/*immunology MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Immunoenzyme Techniques MH - MEF2 Transcription Factors MH - Macrophages/cytology/immunology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - MicroRNAs/*physiology MH - Monocytes/cytology/immunology/metabolism MH - Myeloid Cells/*immunology/metabolism/pathology MH - Myogenic Regulatory Factors/antagonists & inhibitors/genetics/metabolism MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Reactive Oxygen Species/metabolism MH - Receptors, Chemokine/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2011/01/08 06:00 MHDA- 2011/12/13 00:00 CRDT- 2011/01/08 06:00 PHST- 2010/04/28 00:00 [received] PHST- 2010/12/16 00:00 [revised] PHST- 2010/12/23 00:00 [accepted] PHST- 2011/01/08 06:00 [entrez] PHST- 2011/01/08 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] AID - 10.1002/ijc.25921 [doi] PST - ppublish SO - Int J Cancer. 2011 Dec 1;129(11):2662-73. doi: 10.1002/ijc.25921. Epub 2011 Mar 25.