Psoriasis is an immune-mediated chronic inflammatory disease characterized by keratinocyte hyperproliferation and inflammatory cell infiltration. While noncoding RNAs are implicated in its progression, research remains limited. Integrating lncRNA microarray data with LncRNASNP2-based predictions identified the long noncoding RNA (lncRNA) HSFY2-10:1 as a potential functional lncRNA contributing to psoriasis pathogenesis. This study aimed to investigate the role of lnc-HSFY2-10:1/miR-145-5p/fibronectin (FN1) axis in psoriasis. We found that HSFY2-10:1 was significantly upregulated in psoriatic tissues. In a psoriasis cell model established by stimulating NHEKs and HaCaT cells with the M5 cytokine cocktail (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α), lnc-HSFY2-10:1 promoted keratinocyte hyperproliferation and CCL20 secretion. Mechanistically, HSFY2-10:1 functioned as a competitive endogenous RNA for miR-145-5p, thereby regulating FN1 expression. Overexpression of miR-145-5p markedly reversed the HSFY2-10:1-induced upregulation of FN1, keratinocyte proliferation, and CCL20 secretion. These findings indicate that the lnc-HSFY2-10:1/miR-145-5p/FN1 axis plays a crucial role in psoriasis pathogenesis and serves as a potential therapeutic target.
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