miR-17~92 and it’s role in inflammation and innate immune signalling.  — ASN Events

miR-17~92 and it’s role in inflammation and innate immune signalling.  (#176)

James H Stunden 1 , Michael P Gantier 2 , Joachim L Schultze 3 , Eicke Latz 1
  1. Institute for Innate Immunity, Bonn, Germany
  2. Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Vic, Australia
  3. Life and Medical Sciences Institute, University of Bonn, Bonn, Germany

The importance of microRNA regulation of genes is already well accepted, yet we are still to understand the role that miRNA play in the regulation of inflammation. We have previously have shown that miR-19 has pro-inflammatory effects by targeting several negative regulators of NF-kB, and thus resulting in prolonged, chronic inflammatory signalling1. However, miR-19 is also part of the miR-17~92 cluster, a group of miRNA that are transcriptionally activated together, and they may each be able to target many other genes simultaneously.

Our experiments show that miR-19 is induced following LPS treatment in macrophages. Furthermore, removal of the cluster also results in a reduced response to multiple TLR agonists, indicating that the miRNA target more NF-kB signal regulators than previously thought.

We wish to further evaluate the role of these miRNA on the regulation of inflammation, by examining the effect of deleting the whole miRNA cluster in vivo using the miR-17~92flox mouse. We will also examine the effect of deleting the cluster on the transcriptome, by performing a microarray technology to assess which genes are expressed in modified titres from basal levels, which will provide a wealth of information to understand how this miRNA cluster affects the cell.

  1. Gantier, M. P. et al. A miR-19 regulon that controls NF-κB signaling. Nucleic Acids Research 40, 8048–8058 (2012).