CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells

Biomed Res Int. 2015:2015:326042. doi: 10.1155/2015/326042. Epub 2015 Nov 30.

Abstract

MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy
  • CRISPR-Cas Systems / genetics*
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Genome
  • Humans
  • Inositol Polyphosphate 5-Phosphatases
  • Mice
  • MicroRNAs / genetics*
  • Osteoclasts / metabolism
  • Osteogenesis / genetics
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / biosynthesis
  • Phosphoric Monoester Hydrolases / genetics
  • RANK Ligand / biosynthesis
  • RANK Ligand / genetics
  • RNA Editing / genetics*

Substances

  • MicroRNAs
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • INPP5D protein, human
  • Inpp5d protein, mouse
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases