Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression

Sci Rep. 2017 Feb 27:7:43604. doi: 10.1038/srep43604.

Abstract

Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.

MeSH terms

  • Animals
  • Biomarkers
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Self Renewal / genetics*
  • Gene Expression Regulation*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Mice
  • MicroRNAs / genetics*
  • Nerve Tissue Proteins / genetics
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • RNA Interference*
  • RNA-Binding Proteins / genetics
  • Transcription Factor HES-1 / genetics

Substances

  • Biomarkers
  • CCAAT-Enhancer-Binding Protein-beta
  • Interleukin-1beta
  • MIRN155 microRNA, human
  • MSI1 protein, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Transcription Factor HES-1
  • HES1 protein, human