期刊
FEBS JOURNAL
卷 284, 期 15, 页码 2410-2424出版社
WILEY
DOI: 10.1111/febs.14133
关键词
B cell lymphoma; G-MDSCs; miR-30a; M-MDSCs; SOCS3
资金
- Natural Science Foundation of China [91542113, 31370899, 31570909, 81572354, 81402940]
- Natural Science Foundation of Jiangsu Province, China [BK20161400, BK20140615]
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.
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