1. TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7.
- Author
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Min, S, Li, L, Zhang, M, Zhang, Y, Liang, X, Xie, Y, He, Q, Li, Y, Sun, J, Liu, Q, Jiang, X, Che, Y, and Yang, R
- Subjects
TRANSFORMING growth factors ,ENZYME inhibitors ,DENDRITIC cells ,CELL differentiation ,CANCER immunotherapy ,MITOGEN-activated protein kinases ,GENE expression ,TRANSCRIPTION factors ,GENETIC regulation - Abstract
The alterations induced in dendritic cells (DCs) in the cancer microenvironment have not been extensively explored. We found that the tumor-associated factor TGF-β may selectively upregulate the expression of miR-27a via the SP1 transcription factor. Importantly, miR-27a altered the activity of NF-κB and MAPKs (mitogen-activated protein kinases) p38, JNK (c-Jun N-terminal kinases) and ERK (extracellular signal-regulated kinase 1/2). It influences the production of proinflammatory cytokines by targeting TAB3, p38 MAPK, MAP2K4 and MAP2K7. As a consequence, miR-27a hampered the DC-mediated differentiation of Th1 and Th17 cells in vitro and in vivo, but it promoted the DC-mediated accumulation of Tr1 (CD4
+ IL-10+ ) and Treg (CD4+ CD25+ Foxp3+ ) cells in vivo. The repeated infusion of miR-27a-engineered DCs into tumor tissues accelerated tumor growth, indicating that miR-27a is a potential target for tumor immunotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2012
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