银屑病是一种慢性炎症相关的皮肤病，白介素 22 (IL-22) 通过促进角质形成细胞的增殖和迁移参与银屑病的发病机制。越来越多的证据表明，circRNA 可能在银屑病的多个方面发挥重要作用。本研究旨在探讨circ_0056856在调节IL-22诱导的角质形成细胞（HaCaT细胞）表型中的作用和机制。Circ_0056856、microRNA-197-3p（miR-197-3p）、细胞周期蛋白依赖性激酶1（CDK1） ），并使用实时定量聚合酶链反应（RT-qPCR）检测肾母细胞瘤1相关蛋白（WTAP）水平。使用 3-(4, 5-二甲基-2-噻唑基)-2, 5-二苯基-2-H-四唑溴化物 (MTT)、5-乙炔基-2'-脱氧尿苷分析细胞活力、增殖、迁移和侵袭(EdU)、伤口划痕和 Transwell 检测。通过 Circinteractome 或 TargetScan 预测后，通过双荧光素酶报告基因测定验证 miR-197-3p 与 circ_0056856 或 CDK1 之间的结合。使用蛋白质印迹法测定 CDK1 和 WTAP 蛋白水平。使用甲基化 RNA 免疫沉淀 (MeRIP) 测定评估 WTAP 和 circ_0056856 之间的相互作用。在银屑病患者和 IL-22 处理的 HaCaT 细胞中观察到 circ_0056856、CDK1 和 WTAP 增加。此外，circ_0056856敲低可能会抑制IL-22诱导的HaCaT细胞体外增殖、迁移和侵袭。在机制上，circ_0056856可能充当miR-197-3p的海绵来调节CDK1表达，WTAP通过m6A甲基化改善circ_0056856表达。WTAP引导的m6A修饰的circ_0056856通过miR-197-促进IL-22刺激的HaCaT细胞损伤3p/CDK1 轴，可为银屑病治疗提供新颖的见解。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

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).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.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.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.