MicroRNA-125a Correlates with Decreased Psoriasis Severity and Inflammation and Represses Keratinocyte Proliferation

Dermatology. 2021;237(4):568-578. doi: 10.1159/000510681. Epub 2021 Mar 18.

Abstract

Background: Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes.

Methods: Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed.

Results: miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866-0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells.

Conclusion: miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.

Keywords: Disease severity; Keratinocyte; Proinflammatory cytokines; Psoriasis; miR-125a.

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Knockdown Techniques
  • HaCaT Cells
  • Humans
  • Inflammation
  • Interleukin-17 / genetics
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Janus Kinase 2 / metabolism
  • Keratinocytes / physiology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Psoriasis / genetics*
  • Psoriasis / metabolism*
  • Psoriasis / therapy
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Severity of Illness Index
  • Skin / metabolism
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • IL1B protein, human
  • IL23R protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • JAK2 protein, human
  • Janus Kinase 2