MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

J Immunol. 2015 Aug 1;195(3):1301-11. doi: 10.4049/jimmunol.1500209. Epub 2015 Jun 19.

Abstract

Myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-associated immunosuppression, thus affecting effective immunotherapies for cancers. However, the molecular mechanisms involved in regulating the differentiation and function of MDSCs remain largely unclear. In this study, we found that inhibition of microRNA (miR)-9 promoted the differentiation of MDSCs with significantly reduced immunosuppressive function whereas overexpression of miR-9 markedly enhanced the function of MDSCs. Notably, knockdown of miR-9 significantly impaired the activity of MDSCs and inhibited the tumor growth of Lewis lung carcinoma in mice. Moreover, miR-9 regulated MDSCs differentiation by targeting the runt-related transcription factor 1, an essential transcription factor in regulating MDSC differentiation and function. Furthermore, the CREB was found to regulate miR-9 expression in MDSCs. Taken together, our findings have identified a critical role of miR-9 in regulating the differentiation and function of MDSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / immunology
  • Cell Differentiation / genetics
  • Cell Line
  • Core Binding Factor Alpha 2 Subunit / biosynthesis
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Myeloid Cells / cytology*
  • Myeloid Cells / immunology*
  • Promoter Regions, Genetic / genetics
  • beta-Glucans / pharmacology

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • MicroRNAs
  • Mirn92 microRNA, mouse
  • Runx1 protein, mouse
  • beta-Glucans

Associated data

  • GEO/GSE67578