MicroRNA-17-3p is upregulated in psoriasis and regulates keratinocyte hyperproliferation and pro-inflammatory cytokine secretion by targeting <em>CTR9</em>

Eur J Histochem. 2022 Jan 12;66(1):3275. doi: 10.4081/ejh.2022.3275.

Abstract

Psoriasis is a chronic inflammatory skin disease. Although miRNAs are reported to be associated with the pathogenesis of psoriasis, the contribution of individual microRNAs toward psoriasis remains unclear. The miR-17-92 cluster regulates cell growth and immune functions that are associated with psoriasis. miR-17-3p is a member of miR-17-92 cluster; however, its role in dermatological diseases remains unclear. Our study aims at investigating the effects of miR-17-3p and its potential target gene on keratinocytes proliferation and secretion of pro-inflammatory cytokine and their involvement in psoriasis. Initially, we found that miR-17-3p was upregulated in psoriatic skin lesions, and bioinformatic analyses suggested that CTR9 is likely to be a target gene of miR-17-3p. Quantitative reverse-transcriptase PCR and immunohistochemical analysis revealed that CTR9 expression was downregulated in psoriatic lesions. Using dual-luciferase reporter assays, we identified CTR9 as a direct target of miR-17-3p. Further functional experiments demonstrated that miR-17-3p promoted the proliferation and pro-inflammatory cytokine secretion of keratinocytes, whereas CTR9 exerted the opposite effects. Gain-of-function studies confirmed that CTR9 suppression partially accounted for the effects of miR-17-3p in keratinocytes. Furthermore, Western blot revealed that miR-17-3p activates the downstream STAT3 signaling pathway while CTR9 inactivates the STAT3 signaling pathway. Together, these findings indicate that miR-17-3p regulates keratinocyte proliferation and pro-inflammatory cytokine secretion partially by targeting the CTR9, which inactivates the downstream STAT3 protein, implying that miR-17-3p might be a novel therapeutic target for psoriasis.

MeSH terms

  • Cell Proliferation / genetics
  • Cytokines / metabolism
  • Humans
  • Keratinocytes / metabolism
  • MicroRNAs* / metabolism
  • Phosphoproteins / metabolism
  • Phosphoproteins / therapeutic use
  • Psoriasis* / genetics
  • Psoriasis* / metabolism
  • Skin / metabolism
  • Transcription Factors / metabolism

Substances

  • CTR9 protein, human
  • Cytokines
  • MIRN17 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • Transcription Factors