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Brusatol enhances MEF2A expression to inhibit RCC progression through the Wnt signalling pathway in renal cell carcinoma |
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| Authors: | Tao Wang Yu Zhou Hui Bao Bo Liu Min Wang Lei Wang Tiejun Pan |
| Affiliation: | 1. Department of Urology, General Hospital of the Central Theater Command, Wuhan, China;2. Department of Urology, General Hospital of the Central Theater Command, Wuhan, China Contribution: Conceptualization (equal), Investigation (equal), Supervision (equal), Writing - original draft (equal), Writing - review & editing (equal);3. Department of Urology, General Hospital of the Central Theater Command, Wuhan, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal);4. Department of Urology, General Hospital of the Central Theater Command, Wuhan, China Contribution: Supervision (equal), Validation (equal), Visualization (equal);5. Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Project administration (equal), Supervision (equal), Validation (equal) |
| Abstract: | Renal cell carcinoma (RCC) is the most aggressive subtype of kidney tumour with a poor prognosis and an increasing incidence rate worldwide. Brusatol, an essential active ingredient derived from Brucea javanica, exhibits potent antitumour properties. Our study aims to explore a novel treatment strategy for RCC patients. We predicted 37 molecular targets of brusatol based on the structure of brusatol, and MEF2A (Myocyte Enhancer Factor 2A) was selected as our object through bioinformatic analyses. We employed various experimental techniques, including RT-PCR, western blot, CCK8, colony formation, immunofluorescence, wound healing, flow cytometry, Transwell assays and xenograft mouse models, to investigate the impact of MEF2A on RCC. MEF2A expression was found to be reduced in patients with RCC, indicating a close correlation with MEF2A deubiquitylation. Additionally, the protective effects of brusatol on MEF2A were observed. The overexpression of MEF2A inhibits RCC cell proliferation, invasion and migration. In xenograft mice, MEF2A overexpression in RCC cells led to reduced tumour size compared to the control group. The underlying mechanism involves the inhibition of RCC cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) through the modulation of Wnt/β-catenin signalling. Altogether, we found that MEF2A overexpression inhibits RCC progression by Wnt/β-catenin signalling, providing novel insight into diagnosis, treatment and prognosis for RCC patients. |
| Keywords: | Brusatol MEF2A renal cell carcinoma ubiquitylation Wnt/beta-catenin |