Identification of Novel Hub Genes Associated with Psoriasis Using Integrated Bioinformatics Analysis

Abstract

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein–protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell–cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1β. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1β were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.

Topical application of TOPK inhibitor OTS514 suppresses psoriatic progression by inducing keratinocytes cell cycle arrest and apoptosis

“…Inhibiting TOPK decreased keratinocytes proliferation and induced keratinocytes apoptosis, and thereby attenuating psoriasis severity. By using integrated bioinformatics analysis, a recent study by Yue et al reported 10 hub genes that may be associated with psoriasis, and TOPK is one of them 37 . However, Yue et al only provided bioinformatic clues for the possible involvement of TOPK in psoriasis, but they did not conduct further experimental studies on TOPK.…”

Research on the resistance of isoviolanthin to hydrogen peroxide-triggered injury of skin keratinocytes based on Transcriptome sequencing and molecular docking

“…[57] It reported that MCM10 expression was higher in the model group than in the blank control group in the TNF-α induced psoriatic HaCaT cell model. [36] On the whole, these genes abovementioned are involved in DNA replication, mismatch repair, cell cycle, and p53 signaling pathway.…”

“…Among them, the expression trends of KRT16, SPRR1A, SPRR1B, and MCM10 were also consistent with previous literature. [33][34][35][36]…”

Effects of biological agents on glycogen metabolism in psoriasis patients: A systematic review and meta‐analysis

“…Another miRNA, Mir-129-2-3p, that was found to be associated with psoriasis, was engaged in the malfunctioning of diabetic neutrophils. 11,12 These cytokines and genes contribute to the onset of psoriasis, interfere with insulin signalling, and regulate insulin resistance and obesity.…”

“…Most importantly, in transcriptome analysis, many specific genes have revealed the association of psoriasis with MS, such as ACSF2 that is accurate and specific in differentiating psoriasis cases from healthy samples, and impairment of ACSF2 produce is reported to be related to MS and insulin resistance. Another miRNA, Mir‐129‐2‐3p , that was found to be associated with psoriasis, was engaged in the malfunctioning of diabetic neutrophils 11,12 . These cytokines and genes contribute to the onset of psoriasis, interfere with insulin signalling, and regulate insulin resistance and obesity.…”