Wilms' tumor 1-associating protein contributes to psoriasis by promoting keratinocytes proliferation via regulating cyclinA2 and CDK2.

Wilms' tumor 1-associating protein (WTAP) is a ubiquitously expressed nuclear protein, and involved in multiple pathophysiological processes, including cell cycle, RNA splicing and stabilization, N6-methyladenosine RNA modification, cell proliferation, and apoptosis as well as embryonic development. Here, we investigated the specific role of WTAP in the pathogenesis of psoriasis and its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analyses and multi-spectrum immunohistochemistry were applied to evaluate the level of WTAP expression in psoriatic skin and normal skin. HaCaT cells was stably transfected with WTAP small interfering (si)RNA and plasmid using Lipofectamine®2000 and proliferation was determined by CCK8. Apoptosis and cell cycle analysis were conducted by flow cytometry. Western blot assay was used to explore the expression levels of cell cycle-related proteins in HaCaT cells after WTAP overexpression or inhibition. Furthermore, HaCaT cells were stimulated with proinflammatory cytokines (ie, IL-17A, IL-22, IL-1a, oncostatin M, and TNF-a) to assess WTAP expression. We demonstrated that the mRNA and protein levels of WTAP were significantly increased in lesional skins of psoriasis patients and psoriatic cell model compared with normal controls. WTAP was highly expressed in epidermis rather than dermis. Overexpression of WTAP promoted keratinocytes proliferation, which might be related to the up-regulation of cyclinA2 and CDK2. These results indicate that overexpression of WTAP may contribute to the pathogenesis of psoriasis by regulating cell cycle progression and highlight WTAP as a potential therapeutic target for psoriasis treatment.

Kong Y ，Wu R ，Zhang S ，Zhao M ，Wu H ，Lu Q ，Fu S ，Su Y ... -  《-》

WTAP mediated m6A-modified circ_0056856 contributes to the proliferation, migration, and invasion of IL-22-stimulated human keratinocyte by miR-197-3p/CDK1 axis.

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.

Du X ，Shi L ，Wang B ，Zhang G ... -  《-》

Wilms' tumor 1-associating protein promotes renal cell carcinoma proliferation by regulating CDK2 mRNA stability.

Tang J ，Wang F ，Cheng G ，Si S ，Sun X ，Han J ，Yu H ，Zhang W ，Lv Q ，Wei JF ，Yang H ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Overexpression of Wilms' tumor 1 in skin lesions of psoriasis is associated with abnormal proliferation and apoptosis of keratinocytes.

Wu R ，Liao Y ，Shen W ，Liu Y ，Zhang J ，Zheng M ，Chen G ，Su Y ，Zhao M ，Lu Q ... -  《-》

High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m(6)A methylation of MYC mRNA.

Naren D ，Yan T ，Gong Y ，Huang J ，Zhang D ，Sang L ，Zheng X ，Li Y ... -  《-》