MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38

PLoS One. 2015 Mar 31;10(3):e0121510. doi: 10.1371/journal.pone.0121510. eCollection 2015.

Abstract

Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line
  • Dendritic Cells / immunology*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Mirn22 microRNA, mouse
  • p38 Mitogen-Activated Protein Kinases

Grant support

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.