TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7

Genes Immun. 2012 Dec;13(8):621-31. doi: 10.1038/gene.2012.45. Epub 2012 Oct 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • Cell Communication
  • Cell Differentiation
  • Cell Line, Tumor
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MAP Kinase Signaling System
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / pathology
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th17 Cells / drug effects
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*


  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • MIRN27 microRNA, human
  • MicroRNAs
  • TAB3 protein, human
  • Transforming Growth Factor beta
  • Mitogen-Activated Protein Kinases