MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression

Shiyue Mei; Jiaxuan Xin; Yu Liu; Yuan Zhang; Xue Liang; Xiaomin Su; Hui Yan; Yugang Huang; Rongcun Yang

doi:10.1371/journal.pone.0135867

MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression

PLoS One. 2015 Aug 18;10(8):e0135867. doi: 10.1371/journal.pone.0135867. eCollection 2015.

Authors

Shiyue Mei¹, Jiaxuan Xin¹, Yu Liu¹, Yuan Zhang¹, Xue Liang¹, Xiaomin Su¹, Hui Yan¹, Yugang Huang¹, Rongcun Yang²

Affiliations

¹ Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, P. R. China.
² 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.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Line, Tumor
DNA-Binding Proteins / genetics*
Enzyme Activation / drug effects
Enzyme Activation / genetics
Enzyme Activation / immunology
Gene Expression Regulation, Neoplastic / drug effects
Gene Expression Regulation, Neoplastic / genetics*
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Immune Tolerance / drug effects
Immune Tolerance / genetics
Male
Mice
MicroRNAs / genetics*
Myeloid Cells / cytology
Myeloid Cells / drug effects
Myeloid Cells / immunology*
Myeloid Cells / metabolism*
PTEN Phosphohydrolase / genetics*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
STAT3 Transcription Factor / metabolism
Transcription Factors / genetics*

Substances

DNA-Binding Proteins
MicroRNAs
Mirn200 microRNA, mouse
STAT3 Transcription Factor
Transcription Factors
Zfpm2 protein, mouse
Granulocyte-Macrophage Colony-Stimulating Factor
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase

Grants and funding

This research was supported by NSFC grants 31470876, 91029736, 91442111 and ISF-NSFC program 31461143010, a Ministry of Science and Technology grant (863 program, 2008AA02Z129), the National Key Scientific Program (2011CB964902) the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13023) and State Key Laboratory of Medicinal Chemical Biology.