Psoriasis is an autoimmune
skin disease with poor prognosis. Currently, there is no cure for
psoriasis and the pathogenic mechanism of
psoriasis remains unclear. Our study aims to explore key regulators underlying
psoriasis and potential targets for
psoriasis treatment.
RNA-seq data of
psoriasis and normal tissues were extracted from Gene Expression Omnibus database to screen differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) was conducted to identify key gene modules correlated with
psoriasis. Enrichment analysis was used to characterize identified genes. The expression of identified genes was verified in a data set with various types of
psoriasis lesion tissues and six
psoriasis and healthy control tissues by quantitative polymerase chain reaction and immunohistochemistry assays. And the
biological functions of IFIT3 in keratinocytes were determined by colony formation assays, Cell Counting Kit-8, and
enzyme-linked
immunosorbent assays. A total of 594 overlapped genes (370 upregulated and 224 downregulated) were selected as DEGs between
psoriasis and normal tissues in three independent data sets. These genes were enriched in
interferon-related pathway and
cytokine-related pathway. Weighted correlation network analysis identified several gene modules that were associated with
psoriasis. Overlapped genes between gene modules and DEGs were associated with
interferon-related pathway and T cell activities. Among these genes, OAS1, USP18, and IFIT3 had higher expression levels in
psoriasis vulgaris (PV) and nonpustular palmoplantar
psoriasis (
NPPP) tissues but not Palmoplantar Pustular
Psoriasis (
PPPP). Meanwhile, these results were confirmed in our independent
psoriasis tissue cohort. And results of in vitro experiments showed that inhibition of IFIT3 significantly impaired the proliferation capacity and CXCL1, CCL20, IL-1β, and
IL-6 secretion of keratinocytes. Our study identified key genes and pathways underlying the pathogenesis of
psoriasis through the conduct of integrated analysis. OAS1, USP18, and IFIT3 could be potential targets for the treatment of
psoriasis. IFIT3 can promote the proliferation and immune activation of keratinocytes and facilitates the development of
psoriasis.