miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's disease

Biochem Biophys Res Commun. 2013 Aug 16;438(1):133-9. doi: 10.1016/j.bbrc.2013.07.040. Epub 2013 Jul 19.


Crohn's disease (CD) is one of the two major types of inflammatory bowel disease (IBD) thought to be caused by genetic and environmental factors. Recently, miR-122 was found to be deregulated in association with CD progression. However, the underlying molecular mechanisms remain unclear. In the present study, the gene nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly associated with susceptibility to CD, was identified as a functional target of miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. NOD2 interaction with LPS initiates signal transduction mechanisms resulting in the activation of nuclear factor κB (NF-κB) and the stimulation of downstream pro-inflammatory events. The activation of NF-κB was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-α and IFN-γ was significantly decreased, whereas therelease of the anti-inflammatory cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated with miR-122 precursor, NOD2 shRNA or the NF-κB inhibitor QNZ. Taken together, these results indicate that miR-122 and its target gene NOD2 may play an important role in the injury of intestinal epithelial cells induced by LPS.

Keywords: Crohn’s disease (CD); IBD; NOD2; miR-122.

MeSH terms

  • Binding Sites
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology*
  • Down-Regulation
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology*
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • MicroRNAs / metabolism*
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Protein Binding


  • MIRN122 microRNA, human
  • MicroRNAs
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein