Abstract
While NEDD4L is implicated in the onset and progression of various tumors, its role in breast cancer (BRCA) remains unclear. This study aimed to clarify the molecular mechanism behind NEDD4L expression in BRCA and its impact on prognosis. TCGA_BRCA, METABRIC, GSE24450 and GSE42568 data sets were used for gene expression and survival analysis. The riskscore model was developed by LASSO Cox regression, and the nomogram was constructed based on the BRCA riskscore and clinical characters. Cell proliferation and migration were assessed using CCK-8, plate clone formation, and transwell assays. Detection of target genes was achieved using Western blots, immunohistochemistry, and immunofluorescence. Statistical and survival analyses showed that NEDD4L was significantly reduced in BRCA, correlating with poor prognosis. Knockdown of NEDD4L can significantly enhance BRCA cell proliferation and migration. Bioinformatics, cytological experiments, and human BRCA tissue chip analysis reveal that SP1 mediates the reduction of SNAI2 expression in BRCA by promoting NEDD4L expression. The NEDD4L-based LASSO Cox regression model represents an independent prognostic factor. A quantitative evaluation of BRCA prognosis was achieved using a nomogram that integrates risk scores with clinical indicators. This study provides evidence for the SP1/NEDD4L/SNAI2 signal axis mechanism in BRCA, and developed a reliable prognosis model, providing a new target for BRCA therapy. Targeting this axis may lead to innovative treatments, including combination therapies, and help identify new biomarkers for early detection and monitoring of BRCA.
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Data Availability
All data and material relevant to the study available from the corresponding authors upon reasonable request.
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Funding
This study was supported by the Key Scientific and Technological Projects of Henan Province (252102310301), Natural Science Foundation of Henan Province (242300421093), Henan Province College Students’ Innovation Training Project (S202510472043) and Key Scientific Research Projects of Higher Education Institutions in Henan Province (22A180027).
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All authors contributed to the study conception and design. Material preparation was performed by Mengke Wang and Zhuoya Yin; data collection was performed by Yifan Guo, Liping Zhao, Ru Yang, and Binghua Tong; data analysis was performed by Zhenni Guo, Meiqing Sun, Jin Zhao and Huina Zhang. The first draft of the manuscript was written by Baile Zuo Xiaoyan Li and Guoyin Li, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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The Ethics Committee of Shanxi Province People’s Hospital (2021196) approved the use of clinical specimens. Written consent was obtained from all subjects.
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Zuo, B., Li, X., Wang, M. et al. The SP1/NEDD4L Axis Suppresses the Breast Cancer Progression by Downregulating SNAI2 Expression. Biochem Genet (2025). https://doi.org/10.1007/s10528-025-11301-1
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DOI: https://doi.org/10.1007/s10528-025-11301-1