2. Academic Validation
  3. Bisphenol S promotes clear cell renal cell carcinoma progression by modulating the WNT5A-dependent EMT pathway

Bisphenol S promotes clear cell renal cell carcinoma progression by modulating the WNT5A-dependent EMT pathway

  • Toxicology. 2025 Mar 12:514:154117. doi: 10.1016/j.tox.2025.154117.
Hua Zhang 1,  Fei Lin 1,  Bo-Han Lin 1,  Xiong-Lin Sun 1,  Qing-Shui Zheng 1,  Rui Gao 1,  Yong Wei 1,  Shao-Hao Chen 2,  Xue-Yi Xue 3
Affiliations

Affiliations

  • 1 Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
  • 2 Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China. Electronic address: shaohao.chen@fjmu.edu.cn.
  • 3 Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address: xuexueyi@fjmu.edu.cn.
PMID: 40086502 DOI: 10.1016/j.tox.2025.154117
Abstract

Bisphenol S (BPS) is widely used in the production of food containers and children's toys and is known to have endocrine-disrupting effects linked to various cancers; however, its role in renal cell carcinoma (RCC) development remains unclear. This study investigates the mechanisms by which BPS may promote RCC progression. The effects of BPS on proliferation and migration were evaluated in HK-2 and 786-O cells using CCK-8, scratch, and Transwell assays. A LASSO regression model and functional analysis were employed to identify candidate genes involved in BPS-related renal Cancer progression and to construct a prognostic model, which was validated using Kaplan-Meier and ROC curves. Additionally, the impact of BPS on epithelial-mesenchymal transition (EMT)-related markers was examined. Results showed that BPS did not significantly affect the proliferation of HK-2 and 786-O cells at concentrations of 0-10 μM but significantly enhanced cell migration and invasion, inducing EMT. The LASSO model identified nine key genes associated with BPS-related renal Cancer progression, with WNT5A expression positively correlated with BPS concentration. Knockdown of WNT5A significantly inhibited BPS-induced migration of HK-2 and 786-O cells and disrupted the EMT process. These findings demonstrate that BPS promotes HK-2 and 786-O cell migration through the WNT5A-dependent EMT pathway, and inhibition of WNT5A expression can suppress this process. This study provides novel insights into the role of BPS in renal Cancer progression and highlights potential therapeutic targets for RCC.

Keywords

Bisphenol S; Epithelial mesenchymal transition; LASSO regression; Renal cell carcinoma; WNT5A.

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