MicroRNA-720 suppresses M2 macrophage polarization by targeting GATA3

Biosci Rep. 2016 Aug 5;36(4):e00363. doi: 10.1042/BSR20160105. Print 2016 Aug.

Abstract

Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour-associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720 Ectopic expression of GATA3 restored the M2 phenotype in miR-720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function.

Keywords: GATA3; breast cancer; macrophage polarization; microRNA-720.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Female
  • GATA3 Transcription Factor / genetics*
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Primary Cell Culture
  • Signal Transduction
  • THP-1 Cells
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Lipopolysaccharides
  • MIRN720 microRNA, human
  • MicroRNAs
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Tetradecanoylphorbol Acetate