title: miR-223 suppresses differentiation of tumor-induced CD11b⁺ Gr1⁺ myeloid-derived suppressor cells from bone marrow cells.
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.
authors.affiliation: Key Laboratory of Bioactive Materials, Department of Immunology, Ministry of Education, Nankai University School of Medicine, Nankai University, Tianjin, China.
authors.forename: Qiaofei
authors.initials: Q
authors.lastname: Liu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Xingran
authors.initials: X
authors.lastname: Jiang
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Dai
authors.forename: Siping
authors.initials: S
authors.lastname: Min
authors.forename: Xilong
authors.initials: X
authors.lastname: Wu
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: He
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D064326:MEF2 Transcription Factors; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018006:Myogenic Regulatory Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D064326:MEF2 Transcription Factors; C544877:MIRN223 microRNA, mouse; C578041:Mef2c protein, mouse; D035683:MicroRNAs; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine