Psoriasis-Obesity-Related Gene COX7C Promotes Keratinocyte Proliferation and Positively Regulates Inflammatory Responses in Psoriasis.

Obesity (OB) predisposed to psoriasis (PSO) and aggravation of existing PSO. It is a risk factor for PSO and metabolic syndrome. However, the biological link between PSO and OB remains to be studied. The study aimed to explore the relationship between PSO and OB, identify potential predictive biomarkers, and investigate their expression and function in PSO. Mendelian randomization (MR) was used to observe the causal effect between OB and PSO. Using a public database, we identified key shared genes in PSO and OB. Functional enrichment analysis of key shared genes was performed. Single-cell RNA sequencing (ScRNA-seq) analysis was used to further analyse the pivotal biomarkers at the skin cell level in PSO. Motif enrichment analysis was used to screen key transcription factors (TFs). The functional characteristics of PSO skin cell subtypes were evaluated from a metabolic perspective. Two machine learning algorithms were used to screen diagnostic characteristic biomarkers for PSO-OB. The diagnostic efficacy of biomarkers was evaluated by logistic regression analysis and subject's working characteristic curve. Construct a cell model of PSO, and screen the significantly upregulated or downregulated target genes. Knock down the overexpressed target genes using siRNA to investigate their effects on the proliferation and inflammatory response of PSO cells, and clarify their role in the pathogenesis of PSO. MR Analysis showed that OB was a high-risk factor for PSO vulgaris. Nineteen key differentially expressed genes (DEGs) were screened between PSO and OB. Functional enrichment analysis showed that these key DEGs were significantly related to lipid metabolism, thermogenesis and ras signalling pathways. According to ScRNA-seq analysis, psoriatic skin cells were mainly composed of keratinocytes (KC), dendritic cells (DC), macrophages, natural killer cells (NK-cells), T cells, Treg cells and melanoma. Among them, the key DEG of PSO-OB COX7C was significantly correlated and enriched in PSO skin cell development. We identified 24 active transcriptional regulators behind the cellular diversity of psoriatic skin subtypes. We evaluated the role of psoriatic skin cell subtypes in terpenoid backbone biosynthesis, steroid hormone biosynthesis, propanoate metabolism and N-glycan from the perspective of metabolism abundant functions in lipid metabolism such as biosynthesis. Six key genes (AATF, COX7C, GHRH, KCNA3, PCSK1 and PLIN1) obtained by least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithm can be used as promising diagnostic biomarkers for PSO and OB. COX7C significantly upregulates and promotes the proliferation of psoriatic cells while also positively regulating the inflammatory response in PSO. Overall, our study provides a comprehensive assessment of the relationship of potentially key genes in PSO and OB to lipid metabolism, psoriatic skin subtype cells and TFs. COX7C is a diagnostic biomarker for PSO-OB and positively regulates the proliferation and inflammatory response of PSO cells. Which may pave the way for exploring possible associations in the development of these two diseases.