MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression.
Myeloid-derived suppressor cells (MDSCs) constitute one of the major populations that potently suppress anti-tumor immune responses and favor tumor growth in tumor microenvironment. However, the mechanism(s) regulating the differentiation and suppressive function of tumor-associated MDSCs remain(s) unclear. Here, we identified a microRNA-200c (miR-200c), whose expression was dramatically induced by tumor-derived factors. Meanwhile, we also demonstrated that GM-CSF was a main inducer of miR-200c in tumor environment, and miR-200c in turn promoted the expansion and immune suppressive activity of MDSCs via targeting phosphatase and tensin homolog (PTEN) and friend of Gata 2 (FOG2), which can lead to STAT3 and PI3K/Akt activation. Finally, we examined in vivo suppressive function of miR-200c transfected MDSCs and found that miR-200c could remarkably promote tumor growth via modifying MDSCs. Thus, GM-CSF induced miR-200c in tumor environment plays a critical role in governing the expansion and functions of tumor-associated MDSCs and serves as a potential target in immunotherapy against tumor.
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Shiyue
S
Mei
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Jiaxuan
J
Xin
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Yu
Y
Liu
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Yuan
Y
Zhang
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Xue
X
Liang
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Xiaomin
X
Su
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Hui
H
Yan
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
Yugang
Y
Huang
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, P. R. China; Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Rongcun
R
Yang
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; C492170:Zfpm2 protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase