Search

Circular RNAs (circRNAs) are demonstrated to be involved in psoriasis progression. CircRNAs can act as RNA-binding protein (RBP) sponges. Here, we investigated the action of circAKR1B10 in psoriasis, and explored the potential proteins interacted with circAKR1B10. Levels of genes and proteins were assayed by qRT-PCR and western blotting analyses. Keratinocytes in functional groups were treated with interleukin (IL)-22. Functional analysis were conducted using MTT, 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays, respectively. Interaction analysis among circAKR1B10, Eukaryotic initiation factor 4 A-III (EIF4A3) and Aurora Kinase A (AURKA) was conducted using bioinformatics analysis, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. CircAKR1B10 was highly expressed in psoriasis patients and IL-22-induced keratinocytes. Functionally, knockdown of circAKR1B10 abolished IL-22-induced proliferation, migration and invasion in keratinocytes. AURKA expression was also higher in psoriasis patients and IL-22-induced keratinocytes, and was negatively correlated with circAKR1B10 expression. Moreover, AURKA silencing reduced the proliferative, migratory and invasive abilities of IL-22-induced keratinocytes. Mechanistically, circAKR1B10 interacted with EIF4A3 protein to stabilize and regulate AURKA expression. CircAKR1B10 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes via up-regulating AURKA expression through interacting with EIF4A3 protein., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Psoriasis is a chronic inflammation-associated skin disorder, and interleukin-22 (IL-22) is involved in psoriasis pathogenesis by boosting the proliferation and migration of keratinocytes. Mounting evidence has shown that circRNAs might play an important role in several aspects of psoriasis. This study is designed to explore the role and mechanism of circ_0056856 in regulating the phenotypes of IL-22-induced keratinocytes (HaCaT cells)., Methods: Circ_0056856, microRNA-197-3p (miR-197-3p), Cyclin-dependent kinase 1 (CDK1), and Wilms tumor 1-associated protein (WTAP) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, migration, and invasion were analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Wound scratch, and Transwell assays. After being predicted by Circinteractome or TargetScan, binding between miR-197-3p and circ_0056856 or CDK1 was verified by a dual-luciferase reporter assay. CDK1 and WTAP protein levels were determined using Western blot. Interaction between WTAP and circ_0056856 was assessed using methylated RNA immunoprecipitation (MeRIP) assay., Results: Increased circ_0056856, CDK1, and WTAP were observed in psoriasis patients and IL-22-treated HaCaT cells. Moreover, circ_0056856 knockdown might repress IL-22-induced HaCaT cell proliferation, migration, and invasion in vitro. In mechanism, circ_0056856 might function as a sponge of miR-197-3p to modulate CDK1 expression, and WTAP improved circ_0056856 expression via m6A methylation., Conclusion: WTAP-guided m6A modified circ_0056856 facilitates IL-22-stimulated HaCaT cell damage through the miR-197-3p/CDK1 axis, which could provide novel insights into psoriasis treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Psoriasis is an immune-related disease caused by genetic factors, abnormalities in the immune system and environmental factors, while pemphigus is an autoimmune disease caused by the autoimmune system attacking the skin and mucosal tissues. Herein, we aimed to report a rare case of adalimumab induced exacerbation of psoriasis patients with pemphigus. The rare disease causes considerable challenges for clinical diagnosis and treatment., Patient Concerns: The patient was a 43-year-old man with intermittent erythema and scaling all over the body for more than 20 years, and blisters and vesicles on the trunk and limbs for 1 month. Half a year ago, the patient had blisters on the limbs, and was diagnosed with deciduous pemphigus in a hospital, and the blisters subsided after being given traditional Chinese medicine orally. Half a month ago, the erythema area was enlarged, and adalimumab 80 mg intramuscular injection was given for 1 time after consultation in the hospital. On the following day, the area of erythema and scales was suddenly enlarged obviously compared with the previous 1, and obvious blisters and vesicles appeared on the limbs, neck, and trunk, which were aggravated progressively and accompanied by obvious itching and pain., Diagnoses: The patient was diagnosed with psoriasis in patients with combined pemphigus., Intervention: After combined treatment with methylprednisolone and cyclosporine, the skin lesions have basically recovered., Outcomes: The skin lesions have basically healed. Follow up for 6 months without recurrence., Lessons: Methylprednisolone combined with cyclosporine may be an option in treating patients with psoriasis patients with pemphigus., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In a previous large-scale exome sequencing analysis for psoriasis, we discovered seven common and low-frequency missense variants within six genes with genome-wide significance. Here we describe an in-depth analysis of noncoding variants based on sequencing data (10,727 cases and 10,582 controls) with replication in an independent cohort of Han Chinese individuals consisting of 4,480 cases and 6,521 controls to identify additional psoriasis susceptibility loci. We confirmed four known psoriasis susceptibility loci (IL12B, IFIH1, ERAP1 and RNF114; 2.30 × 10(-20)≤P≤2.41 × 10(-7)) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10(-8)), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10(-8)) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10(-8)). Two suggestive loci, 3p21.31 and 17q25, are also identified with P<1.00 × 10(-6). The results of this study increase the number of confirmed psoriasis risk loci and provide novel insight into the pathogenesis of psoriasis.

This study aimed to identify hub genes and common pathways shared between psoriasis and cardiovascular disease (CVD) using bioinformatics analysis and predict the transcription factors (TFs) of hub genes.Methods: GSE133555 data from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) between involved and uninvolved skin lesions in psoriasis, employing the limma package in R. Additionally, CVD-related genes were obtained from the GeneCards database. The intersection of DEGs and CVD-related genes yielded CVD-DEGs. Gene Ontology and signaling pathway analyses were performed using the clusterProfiler package in R. Hub genes were identified by intersecting six algorithms in the CytoHubba plugin of Cytoscape. To identify potential biomarkers, the GSE14905 dataset was subjected to receiver operating characteristic analysis, resulting in the identification of eight central hub genes. Finally, the NetworkAnalyst web tool was used to identify the TFs of the eight hub genes.Results: We identified 92 significant DEGs out of 1825 CVD-related genes in psoriasis obtained from the GSE13355 and GeneCard data. Functional enrichment analysis revealed the involvement of these genes in various signaling pathways, including the interleukin-17 signaling, tumor necrosis factor signaling, lipid and atherosclerosis, chemokine signaling, and cytokine signaling pathways in the immune system. The eight hub genes identified included interleukin-1 beta, C-X-C motif chemokine ligand 8, signal transducer and activator of transcription 3, C-C motif chemokine ligand 2, arginase 1, C-X-C motif chemokine receptor 4, cyclin D1, and matrix metallopeptidase 9, with forkhead box C1 also identified as an associated TF of these genes. These hub genes and TF may act as key regulators in the context of CVD.Conclusion: This study identified several hub genes and signaling pathways associated with both CVD and psoriasis. These findings lay the groundwork for potential therapeutic interventions for patients with psoriasis affected by CVD. [ABSTRACT FROM AUTHOR]