Expression of microRNA-184 in keratinocytes represses argonaute 2

J Cell Physiol. 2013 Dec;228(12):2314-23. doi: 10.1002/jcp.24401.

Abstract

Interleukin-22 (IL-22) is a proinflammatory cytokine that has been associated with the pathogenesis of inflammatory skin disorders. However, the impact of IL-22 on microRNA (miRNA) expression in epidermal keratinocytes is unknown. Here we show that IL-22 induces miR-184 in reconstituted human epidermis (RHE) and in the HaCaT keratinocyte cell line. Exposure to IL-22 increased miR-184 expression 8- and 15-fold in RHE and HaCaT cells, respectively. Oncostatin M, an unrelated proinflammatory cytokine, also raised miR-184 expression in RHE and HaCaT keratinocytes. Pharmacologic and genetic inhibition demonstrated that cytokine-induced expression of miR-184 was mediated by signal transducer and activation of transcription 3 (STAT3). Argonaute 2 (AGO2), a member of the RNA-induced silencing complex (RISC), is a predicted miR-184 target. Using protein, messenger RNA and reporter analyses, we found that miR-184 regulates the expression of AGO2. We conclude that cytokine-induced miR-184 attenuates AGO2 expression in keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism*
  • Cell Line
  • Down-Regulation / genetics
  • Epidermis / metabolism
  • Humans
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / metabolism
  • Keratinocytes / metabolism*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Psoriasis / genetics
  • Psoriasis / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Interleukins
  • MIRN184 microRNA, human
  • MicroRNAs
  • RNA-Induced Silencing Complex
  • STAT3 Transcription Factor
  • STAT3 protein, human