神经前体细胞表达发育下调样蛋白4调控Wnt/β-catenin通路对急性髓系白血病细胞增殖和凋亡的影响

doi:10.3969/j.issn.1006-5725.2026.14.006

Abstract

Abstract:

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.

Key words: NEDD4L, Wnt/β-catenin pathway, acute myeloid meukemia, cell proliferation, cell apoptosis

CLC Number:

R733.7

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.

Figures/Tables 7

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Effect of NEDD4L on proliferation and apoptosis of acute myeloid leukemia cells via the Wnt/β-catenin pathway

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