Psoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated in both psoriatic lesion samples and HaCaT cell lines in response to IL-22 treatment. After SPRR2C knockdown, IL-22-induced suppression of HaCaT proliferation, changes in the KRT5/14/1/10 protein levels, and suppression of the IL-1β, IL-6, and TNF-α mRNA levels were dramatically reversed. In the coexpression network with SPRR2C based on GSE114286, miR-330 was significantly negatively correlated with SPRR2C, while STAT1 and S100A7 were positively correlated with SPRR2C. By binding to miR-330, SPRR2C competed with STAT1 and S100A7 to counteract miR-330-mediated suppression of STAT1 and S100A7. MiR-330 overexpression also reversed the IL-22-induced changes in HaCaT cell lines; in response to IL-22 treatment, miR-330 inhibition significantly attenuated the effects of SPRR2C knockdown. STAT1 and S100A7 expression was significantly upregulated in psoriatic lesion samples. The expression of miR-330 had a negative correlation with the expression of SPRR2C, while the expression of SPRR2C had a positive correlation with the expression of STAT1 and S100A7. Thus, SPRR2C modulates the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis. WGCNA might uncover additional biological pathways that are crucial in the pathogenesis and response to the treatment of psoriasis.

牛皮癣是一种发病机制高度复杂的慢性皮肤炎症性疾病。在这项研究中，我们使用加权基因共表达网络分析 (WGCNA) 和差异表达分析，确定了 lncRNA SPRR2C（富含脯氨酸的小蛋白 2C）作为一个中心基因，对银屑病的发病机制和治疗反应具有关键影响。 IL-22 治疗后，银屑病病变样本和 HaCaT 细胞系中 SPRR2C 表达显着上调。 SPRR2C 敲低后，IL-22 诱导的 HaCaT 增殖抑制、KRT5/14/1/10 蛋白水平的变化以及 IL-1β、IL-6 和 TNF-α mRNA 水平的抑制均显着逆转。在基于GSE114286的与SPRR2C的共表达网络中，miR-330与SPRR2C显着负相关，而STAT1和S100A7与SPRR2C正相关。通过与 miR-330 结合，SPRR2C 与 STAT1 和 S100A7 竞争，抵消 miR-330 介导的 STAT1 和 S100A7 抑制。 MiR-330 过表达还逆转了 HaCaT 细胞系中 IL-22 诱导的变化；作为对 IL-22 治疗的反应，miR-330 抑制显着减弱了 SPRR2C 敲低的效果。银屑病病变样本中 STAT1 和 S100A7 表达显着上调。 miR-330的表达量与SPRR2C的表达量呈负相关,SPRR2C的表达量与STAT1、S100A7的表达量呈正相关。因此，SPRR2C 通过 miR-330/STAT1/S100A7 轴调节 IL-22 刺激的 HaCaT 细胞表型。 WGCNA 可能会发现在银屑病的发病机制和治疗反应中至关重要的其他生物学途径。