RBM15-Mediated m6A Modification of K17 Affects Keratinocytes Response to IL-17A Stimulation in Psoriasis

Manni Fu1, Bei Zhou1, Nian Shi1

  • 1Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China.

Abstract

Insights

RNA-binding motif protein 15 (RBM15) regulates psoriasis by controlling keratinocyte proliferation and inflammation. RBM15 knockdown reduces Keratin 17 (K17) mRNA stability via m6A modification, offering new psoriasis treatment insights.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Epigenetics

Background:

  • Psoriasis involves keratinocyte hyperproliferation and abnormal differentiation.
  • Interleukin-17A (IL-17A) plays a key role in psoriasis pathogenesis.
  • N6-methyladenosine (m6A) modification is increasingly recognized in skin diseases.

Purpose of the Study:

  • To investigate the function and mechanism of RNA-binding motif protein 15 (RBM15) in IL-17A-induced keratinocytes.
  • To explore the role of RBM15 in psoriasis pathogenesis.

Main Methods:

  • Utilized HaCaT keratinocyte cell line with IL-17A stimulation.
  • Assessed mRNA and protein levels via qRT-PCR and Western blotting.
  • Quantified keratinocyte proliferation (CCK8, EdU) and inflammation (IL-8, TNF-α).
  • Confirmed m6A modification of Keratin 17 (K17) using MeRIP and mRNA stability assays.

Main Results:

  • RBM15 and K17 were upregulated in psoriasis and IL-17A-stimulated keratinocytes.
  • RBM15 silencing suppressed keratinocyte viability, proliferation, and inflammation.
  • RBM15 knockdown decreased K17 mRNA stability through m6A modification.
  • K17 overexpression counteracted the effects of RBM15 knockdown.

Conclusions:

  • RBM15 knockdown inhibits keratinocyte proliferation and inflammation by reducing K17 mRNA stability via m6A modification.
  • RBM15 acts as a key regulator in IL-17A-induced keratinocyte responses.
  • Findings suggest RBM15 as a potential therapeutic target for psoriasis.

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