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. 2025 Jun;83(2):2101-2113.
doi: 10.1007/s12013-024-01620-2. Epub 2024 Nov 20.

TOP2A Promotes Proliferation, Migration, and Inflammatory Response in M5-Treated Keratinocytes by Binding CTBP1 to Activate Wnt/β-Catenin Signaling

Yuanwen Yang  1 , Shumei Liu  2 , Xia Xiao  3
Affiliations

TOP2A Promotes Proliferation, Migration, and Inflammatory Response in M5-Treated Keratinocytes by Binding CTBP1 to Activate Wnt/β-Catenin Signaling

Yuanwen Yang et al. Cell Biochem Biophys. 2025 Jun.

Abstract

Psoriasis is a chronic cutaneous disease, affecting a significant portion of the global population. Topoisomerase II alpha (TOP2A) is upregulated in psoriasis samples, but the precise molecular mechanism remains unclear. We aimed to clarify the biological contribution of TOP2A in psoriasis progression. An in vitro psoriasis model was established on M5-induced keratinocytes (HaCaT cells) to simulate the psoriasis-like alterations. Following TOP2A knockdown without or with c terminal binding protein 1 (CTBP1) overexpression, CCK-8 and EDU staining were employed to analyze the viability and proliferation of HaCaT cells under M5 conditions. The capacities of HaCaT cell migration and invasion were examined with wound healing- and transwell assays. RT-qPCR and immunoblotting were adopted for evaluation of the inflammation and differentiation of M5-stimualted HaCaT cells. Additionally, the binding between TOP2A and CTBP1 was predicated using bioinformatics tools and detected by Co-IP. Finally, the expression of proteins in Wnt/β-catenin signaling was analyzed with the application of immunoblotting. Results suggested that TOP2A was upregulated in psoriasis skin lesions and M5-induced HaCaT cells. Interference with TOP2A attenuated the proliferation, migration, invasion, and inflammatory response in M5-treated HaCaT cells. In particular, TOP2A bound to CTBP1 and upregulated CTBP1 expression in HaCaT cells. Remarkably, CTBP1 upregulation blocked the impacts of TOP2A depletion on the biological behaviors of M5-treated HaCaT cells. Besides, TOP2A deficiency upregulated DKK1 expression as well as downregulated Wnt1, β-catenin, and c-Myc expression in HaCaT cells exposed to M5, which was restored by further CTBP1 overexpression. In summary, TOP2A binds CTBP1 to activate Wnt/β-catenin signaling, thereby promoting the progression of psoriasis.

Keywords: Inflammation; Migration; Psoriasis; TOP2A; Wnt/β-catenin signaling.

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Conflict of interest statement

Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests.

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