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Brusatol enhances MEF2A expression to inhibit RCC progression through the Wnt signalling pathway in renal cell

Tao Wang1, Yu Zhou1, Hui Bao1

  • 1Department of Urology, General Hospital of the Central Theater Command, Wuhan, China.

Journal of Cellular and Molecular Medicine
|October 20, 2023
PubMed

Insights

Myocyte enhancer factor 2A (MEF2A) overexpression inhibits renal cell carcinoma (RCC) progression. This study reveals MEF2A

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Renal cell carcinoma (RCC) is an aggressive kidney tumor with increasing incidence and poor prognosis.
  • Brusatol, derived from Brucea javanica, shows potent antitumour properties.
  • Identifying novel therapeutic targets for RCC is crucial.

Purpose of the Study:

  • To investigate the role of Myocyte Enhancer Factor 2A (MEF2A) in renal cell carcinoma (RCC).
  • To explore brusatol's protective effects on MEF2A in RCC.
  • To elucidate the underlying molecular mechanisms of MEF2A in inhibiting RCC progression.

Main Methods:

  • Bioinformatic analysis to identify brusatol targets, selecting MEF2A.
  • In vitro assays (RT-PCR, Western blot, CCK8, colony formation, immunofluorescence, wound healing, flow cytometry, Transwell) and in vivo xenograft mouse models.
  • Investigation of MEF2A expression, deubiquitylation, and its impact on Wnt/β-catenin signaling.

Main Results:

  • MEF2A expression is reduced in RCC patients and correlates with deubiquitylation.
  • Brusatol demonstrated protective effects on MEF2A.
  • MEF2A overexpression inhibited RCC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), reducing tumor size in mice via Wnt/β-catenin signaling modulation.

Conclusions:

  • MEF2A functions as a tumor suppressor in RCC.
  • MEF2A overexpression inhibits RCC progression through the Wnt/β-catenin signaling pathway.
  • MEF2A represents a potential diagnostic marker and therapeutic target for RCC.
Keywords:
BrusatolMEF2AWnt/beta-cateninrenal cell carcinomaubiquitylation

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