The Journal of Practical Medicine >
Effect of NEDD4L on proliferation and apoptosis of acute myeloid leukemia cells via the Wnt/β-catenin pathway
Received date: 2026-03-24
Online published: 2026-08-05
Objective To investigate the effect of NEDD4L on the proliferation and apoptosis of acute myeloid leukemia (AML) cells and its underlying mechanism via the regulation of the Wnt/β-catenin pathway. Methods Stable NEDD4L-overexpressing and NEDD4L-knockdown Kasumi-1 and U937 cell lines were successfully established via lentiviral transduction technology. The efficiency of NEDD4L overexpression and knockdown was rigorously verified by RT-qPCR and Western blot. Cell proliferation was accurately assessed using the CCK-8 assay, and apoptosis was precisely detected through flow cytometry. The expression levels of the apoptosis-related proteins BAX and Bcl2, along with the key proteins of the Wnt/β-catenin pathway (β-catenin, c-Myc, and cyclin D1), were measured by Western blot. Results Results from RT-qPCR and Western blot assays demonstrated that NEDD4L was successfully overexpressed and knocked down in Kasumi-1 and U937 cell lines (P < 0.05). CCK-8 assay results indicated that overexpression of NEDD4L significantly inhibited the proliferative capacity of Kasumi-1 and U937 cells (P < 0.05). Flow cytometry results showed that overexpression of NEDD4L significantly increased the apoptosis rate in Kasumi-1 and U937 cells. Western blot analysis results revealed that overexpression of NEDD4L upregulated the pro-apoptotic protein BAX and downregulated the anti-apoptotic protein Bcl2 (P < 0.05). Mechanistic studies results showed that overexpression of NEDD4L decreased the expression of β-catenin, c-Myc, and cyclin D1, whereas knockdown of NEDD4L upregulated these proteins. Furthermore, the Wnt/β-catenin pathway agonist SKL2001 partially reversed the pathway inhibition induced by overexpression of NEDD4L (P < 0.05). Conclusion NEDD4L inhibits the proliferation of AML cells and induces the apoptosis of AML cells by suppressing the activity of the Wnt/β-catenin pathway, which suggests that NEDD4L may serve as a potential therapeutic target for AML.
Yuancheng LIU , Chenglong HU , Wu ZHOU , Jingxin ZHANG , Qinglin ZHANG , Huali HU , Sixi WEI . Effect of NEDD4L on proliferation and apoptosis of acute myeloid leukemia cells via the Wnt/β-catenin pathway[J]. The Journal of Practical Medicine, 2026 , 42(14) : 2533 -2541 . DOI: 10.3969/j.issn.1006-5725.2026.14.006
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