Involvement of miR-214-3p/FOXM1 Axis During the Progression of Psoriasis

Inflammation. 2022 Feb;45(1):267-278. doi: 10.1007/s10753-021-01544-6. Epub 2021 Aug 24.

Abstract

Psoriasis is a common, chronic, and relapsing skin disease characterized by hyperproliferation of keratinocytes and apoptosis delay. However, the molecular mechanisms underlying the progression of psoriasis remain elusive. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play a crucial role in the development of psoriasis by promoting targeted mRNA degradation or translational inhibition. Here, we report that miR-214-3p, one of the downregulated miRNAs identified in the skin of psoriatic patients and imiquimod (IMQ)-induced mouse models, can negatively regulate the expression of forkhead box M1 (FOXM1). miR-214-3p inhibition leads to hyperproliferation and increased apoptosis of keratinocytes in vitro. Moreover, we show that miR-214-3p inhibition causes an arrest of the cell cycle at the S stage by elevating the expression of NEK2, KIF20A, CENP-A, CENP-F, and Cyclin B1 and by reducing the expression of Cyclin D1 in HaCaT cells. In vivo, the administration of miR-214-3p attenuates the psoriasis-like phenotype in IMQ-induced mice. Collectively, our results suggest that miR-214-3p/FOXM1 axis in keratinocytes could be a novel target in the treatment of psoriasis.

Keywords: FOXM1;; keratinocytes.; miR-214-3p;; psoriasis;.

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Disease Progression
  • Forkhead Box Protein M1 / metabolism*
  • Humans
  • Mice
  • Mice, Inbred ICR
  • MicroRNAs / metabolism*
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Psoriasis / physiopathology

Substances

  • Biomarkers
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Foxm1 protein, mouse
  • MIRN214 microRNA, human
  • MicroRNAs
  • Mirn214 microRNA, mouse