MiR-30a increases MDSC differentiation and immunosuppressive function by targeting SOCS3 in mice with B-cell lymphoma

Zhen Xu; Jianjian Ji; Jingjing Xu; Dan Li; Guoping Shi; Fei Liu; Liang Ding; Jing Ren; Huan Dou; Tingting Wang; Yayi Hou

doi:10.1111/febs.14133

MiR-30a increases MDSC differentiation and immunosuppressive function by targeting SOCS3 in mice with B-cell lymphoma

FEBS J. 2017 Aug;284(15):2410-2424. doi: 10.1111/febs.14133. Epub 2017 Jul 21.

Authors

Zhen Xu¹, Jianjian Ji¹, Jingjing Xu¹, Dan Li¹, Guoping Shi¹, Fei Liu¹, Liang Ding¹, Jing Ren¹, Huan Dou^{1

2}, Tingting Wang^{1

2}, Yayi Hou^{1

2}

Affiliations

¹ The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
² Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.

PMID: 28605567
DOI: 10.1111/febs.14133

Abstract

Myeloid-derived suppressor cells (MDSCs), including granulocytic (G)-MDSCs and monocytic (M)-MDSCs, play a critical role in tumor-induced T cell tolerance. MDSC immunosuppressive function and differentiation are significantly promoted in patients and B-cell lymphoma model mice. However, the mechanisms regulating these processes remain largely unclear. In the present study, we observed increased microRNA (miR)-30a expression both in G-MDSCs and in M-MDSCs from B cell lymphoma model mice. After transfection with miR-30a mimics, the differentiation and suppressive capacities of MDSCs were significantly increased via up-regulation of arginase-1. Moreover, we showed that the 3'-UTR of suppressor of cytokine signaling 3 (SOCS3) mRNA is a direct target of miR-30a. Decreased SOCS3 expression and activated Janus kinase-signal transducer and activator of transcription 3 signaling promote MDSC differentiation and suppressive activities. These findings provide new insights into the molecular mechanisms underlying MDSC expansion and function during B cell lymphoma development.

Keywords: B cell lymphoma; G-MDSCs; M-MDSCs; SOCS3; miR-30a.

Publication types

Comparative Study

MeSH terms

3' Untranslated Regions*
Animals
Arginase / genetics
Arginase / metabolism
Bone Marrow Cells / pathology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / pathology
Cell Differentiation*
Cell Line, Tumor
Cells, Cultured
Gene Expression Regulation, Neoplastic
Granulocyte Precursor Cells / immunology
Granulocyte Precursor Cells / metabolism
Granulocyte Precursor Cells / pathology
Immunosuppression Therapy
Lymphoma, B-Cell / immunology
Lymphoma, B-Cell / metabolism*
Lymphoma, B-Cell / pathology
Lymphoma, B-Cell / therapy
Mice
Mice, Inbred BALB C
MicroRNAs / antagonists & inhibitors
MicroRNAs / metabolism*
Monocyte-Macrophage Precursor Cells / immunology
Monocyte-Macrophage Precursor Cells / metabolism
Monocyte-Macrophage Precursor Cells / pathology
Myeloid-Derived Suppressor Cells / cytology
Myeloid-Derived Suppressor Cells / immunology
Myeloid-Derived Suppressor Cells / metabolism*
Myeloid-Derived Suppressor Cells / pathology
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Neoplasm Transplantation
Spleen / pathology
Suppressor of Cytokine Signaling 3 Protein / genetics
Suppressor of Cytokine Signaling 3 Protein / metabolism*
Up-Regulation*

Substances

3' Untranslated Regions
MicroRNAs
Mirn30d microRNA, mouse
Neoplasm Proteins
Socs3 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Arg1 protein, mouse
Arginase