CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway

Exp Dermatol. 2022 Aug;31(8):1145-1153. doi: 10.1111/exd.14565. Epub 2022 Mar 18.

Abstract

Psoriasis is a chronic, immune-mediated skin disease accompanied by hyperproliferation and inflammation of keratinocytes. Circular RNAs (circRNAs) as new players regulating the development of psoriasis have been reported in recent years. However, its mechanism has not yet been fully revealed. In this study, we identified that hsa_circ_0033469 (circEIF5) was highly expressed in psoriasis tissues compared with the normal skin. We investigated the functional roles of circEIF5 in proliferation and inflammatory of HaCat cells under M5-stimulated inflammatory condition. By using a approach of knockdown and overexpression of circEIF5, we showed that circEIF5 could promote proliferation by facilitating the G1/S transition and increase secretion of chemokines in HaCat cells. These moderating effects of circEIF5 were associated with the activating of the NF-κB and STAT3 signalling pathways. Moreover, NF-κB and STAT3 inhibition abrogated circEIF5-induced promotion of cell proliferation and chemokine secretion. These results indicated that through NF-κB and STAT3 signalling pathways, circEIF5 regulated the proliferation and chemokine secretion of HaCat cells and contributed to the pathogenesis of psoriasis, which might become a potent target for psoriasis treatment.

Keywords: chemokine; circEIF5; keratinocytes; proliferation; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Humans
  • Inflammation / metabolism
  • Keratinocytes / metabolism
  • NF-kappa B* / metabolism
  • Peptide Initiation Factors / genetics
  • Psoriasis* / metabolism
  • RNA, Circular
  • STAT3 Transcription Factor / metabolism

Substances

  • NF-kappa B
  • Peptide Initiation Factors
  • RNA, Circular
  • STAT3 Transcription Factor
  • STAT3 protein, human