Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

Oncotarget. 2016 Jul 12;7(28):43076-43087. doi: 10.18632/oncotarget.9246.


Cancer secreted exosomal miRNAs are emerging as mediators between tumor-stoma crosstalk. Here, we show epithelial ovarian cancer (EOC)-derived exosomes activated macrophages to a tumor-associated macrophage (TAM)-like phenotype with SOCS3/STAT3 pathway involvement, which could facilitate the progression of cancer. MiR-222-3p was enrichment in exosomes released from EOC cells and it could be transferred to macrophages. Overexpression of miR-222-3p in macrophages induced polarization of the M2 phenotype. Luciferase assay verified miR-222-3p targeted SOCS3 genes and expression of SOCS3 was decreased after transfection with a miR-222-3p mimic. Down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. MiR-222-3p could be detected in the exosomes from serum and its levels were related to EOC. These observations propose tumor-derived exosomal miR-222-3p is an effective regulator in the polarization of tumor-promoting M2 macrophages and may be a biomarker of EOC.

Keywords: epithelial ovarian cancer; exosomes; macrophage; miR-222-3p; polarization.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Down-Regulation
  • Exosomes / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Macrophage Activation / genetics*
  • Macrophages / metabolism*
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasms, Glandular and Epithelial / blood
  • Neoplasms, Glandular and Epithelial / genetics*
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • STAT3 Transcription Factor / genetics
  • Suppressor of Cytokine Signaling 3 Protein / genetics
  • Transplantation, Heterologous
  • U937 Cells


  • Biomarkers, Tumor
  • MIRN222 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 3 Protein