MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40

J Immunol. 2013 Jan 15;190(2):678-88. doi: 10.4049/jimmunol.1202695. Epub 2012 Dec 10.


Psoriasis is characterized by a specific microRNA expression profile, distinct from that of healthy skin. MiR-31 is one of the most highly overexpressed microRNAs in psoriasis skin; however, its biological role in the disease has not been studied. In this study, we show that miR-31 is markedly overexpressed in psoriasis keratinocytes. Specific inhibition of miR-31 suppressed NF-κB-driven promoter luciferase activity and the basal and TNF-α-induced production of IL-1β, CXCL1/growth-related oncogene-α, CXCL5/epithelial-derived neutrophil-activating peptide 78, and CXCL8/IL-8 in human primary keratinocytes. Moreover, interference with endogenous miR-31 decreased the ability of keratinocytes to activate endothelial cells and attract leukocytes. By microarray expression profiling, we identified genes regulated by miR-31 in keratinocytes. Among these genes, we identified serine/threonine kinase 40 (STK40), a negative regulator of NF-κB signaling, as a direct target for miR-31. Silencing of STK40 rescued the suppressive effect of miR-31 inhibition on cytokine/chemokine expression, indicating that miR-31 regulates cytokine/chemokine expression via targeting STK40 in keratinocytes. Finally, we demonstrated that TGF-β1, a cytokine highly expressed in psoriasis epidermis, upregulated miR-31 expression in keratinocytes in vitro and in vivo. Collectively, our findings suggest that overexpression of miR-31 contributes to skin inflammation in psoriasis lesions by regulating the production of inflammatory mediators and leukocyte chemotaxis to the skin. Our data indicate that inhibition of miR-31 may be a potential therapeutic option in psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokines / biosynthesis
  • Chemotaxis, Leukocyte / immunology
  • Cytokines / biosynthesis*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation
  • Gene Expression*
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Keratinocytes / metabolism*
  • MicroRNAs / genetics*
  • NF-kappa B
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Psoriasis / enzymology
  • Psoriasis / genetics*
  • Psoriasis / immunology*
  • RNA Interference
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism


  • Chemokines
  • Cytokines
  • Inflammation Mediators
  • MIRN31 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • STK40 protein, human

Associated data

  • GEO/GSE41905