Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis

J Cell Physiol. 2019 Apr;234(4):3661-3674. doi: 10.1002/jcp.27135. Epub 2018 Sep 14.

Abstract

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. However, the pathogenesis of psoriasis is multifactorial and is not fully understood. MicroRNAs (miRNAs) represent a promising class of small, noncoding RNA molecules that have a large impact on cellular functions by regulating gene expression. Here we reported that microRNA-187 (miR-187), which is one of the most dynamic microRNAs identified in the deep screening miRNAs profile, is downregulated in inflammatory cytokines-stimulated keratinocytes and psoriatic skins. By luciferase activity assay and gain-of-function studies, we showed that miR-187 inhibits keratinocytes hyperproliferation by targeting CD276. Moreover, overexpression of miR-187 decreases acanthosis and reduces the disease severity in psoriasis mouse models. Taken together, the results of our study implies miR-187 as a critical factor in psoriasis pathogenesis, which could be a potent target for psoriasis treatment.

Keywords: CD276; epidermal hyperplasia; keratinocytes hyperproliferation; microRNA‐187 (miR‐187); psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7 Antigens / genetics
  • B7 Antigens / metabolism
  • Case-Control Studies
  • Cell Line
  • Cell Proliferation* / drug effects
  • Cytokines / pharmacology
  • Disease Models, Animal
  • Down-Regulation
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Psoriasis / genetics
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Psoriasis / prevention & control
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / pathology

Substances

  • B7 Antigens
  • CD276 protein, human
  • Cytokines
  • MIRN187 microRNA, human
  • MicroRNAs