MiR-200b modulates the properties of human monocyte-derived dendritic cells by targeting WASF3

Life Sci. 2015 Feb 1:122:26-36. doi: 10.1016/j.lfs.2014.11.023. Epub 2014 Dec 13.

Abstract

Aims: The aim of the study was to explore the effect of miR-200b on the development of human peripheral blood monocyte-deriveddendritic-cell (DC) and its mechanisms.

Main methods: Expression levels of miR-200b and its predicted targets were measured by real time-PCR. Protein expression of WASF3 was determined by Western blot and immunohistochemistry. Human peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient centrifugation from the buffy coat fraction of anticoagulated blood. Monocytes were purified from PBMCs using anti-CD14 microbeads. The immunophenotypes of DCs were tested by flow cytometry.

Key findings: A strong reduction in miR-200b expression was associated with human peripheral blood monocyte-derivedDC differentiation. The overexpression of miR-200b significantly reduced the numbers of protruding veils in mature DCs (mDCs) that are critical for promoting antigen-specificT-cell activation. Further experiments showed that miR-200b could regulate the function of DCs by targeting WASF3, a protein involved in cell movement and invasion.

Significance: Our results define an important function of miR-200b in the negative regulation of DC development and provide a potential form of miRNA-mediated cell therapy for diseases that range from auto-immunity to graft-versus-host disease.

Keywords: Dendritic cell; Human monocyte; MiR-200b; WASF3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Movement
  • Cell Proliferation*
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • Humans
  • Immunoenzyme Techniques
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism*
  • MicroRNAs / physiology*
  • Monocytes / cytology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wiskott-Aldrich Syndrome Protein Family / antagonists & inhibitors
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • WASF3 protein, human
  • Wiskott-Aldrich Syndrome Protein Family