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Journal of Cancer Research and Clinical Oncology

E3 ubiquitin ligase BTRC inhibits the proliferation and tumor growth of glioma cells through the NFAT5/AQP4 axis

  • Open Access
  • 01-12-2025
  • Research
Published in:
Authors
Yexin Li
Siqiang Tang
Kaiyuan Jiang
Peng Deng
Xiqi Hu
Published in
Journal of Cancer Research and Clinical Oncology | Issue 12/2025

Abstract

Objective

Ubiquitination is integral to the pathogenesis of various tumors. This study sought to elucidate the role and underlying mechanisms of BTRC-mediated ubiquitination and degradation in glioma.

Method

The expression levels of beta-transduced in repeat containing E3 ubiquitin protein ligase (BTRC), nuclear factor of activated T cells 5 (NFAT5) and aquaporin-4 (AQP4) were assessed by RT-qPCR/Western blot. The association and underlying mechanisms of BTRC, NFAT5, and AQP4 were examined through co-immunoprecipitation, cycloheximide chase, and chromatin immunoprecipitation assays. The influence of the BTRC/NFAT5/AQP4 axis on the malignant biological functions of glioma cells and tumor growth was evaluated through a series of in vitro and in vivo experiments.

Results

In glioma cells, BTRC expression was observed to be downregulated. Overexpression of BTRC inhibits proliferation, migration and invasion, while promoting apoptosis in glioma cells. Mechanically, BTRC overexpression facilitates ubiquitination and degradation of NFAT5, thereby inhibiting NFAT5-mediated transcriptional activation of AQP4. Functional recovery assays demonstrated that the overexpression of either AQP4 or NFAT5 counteracted the intervention effect of upregulation of BTRC on the malignant behavior of glioma cells. In vivo animal experiments further confirmed the results of the in vitro experiments, indicating that the overexpression of BTRC inhibits tumor growth through the NFAT5/AQP4 axis.

Conclusion

BTRC negatively modulates the transcription of AQP4 via NFAT5 in glioma cells, thereby influencing their malignant biological functions and tumor growth.
Title
E3 ubiquitin ligase BTRC inhibits the proliferation and tumor growth of glioma cells through the NFAT5/AQP4 axis
Authors
Yexin Li
Siqiang Tang
Kaiyuan Jiang
Peng Deng
Xiqi Hu
Publication date
01-12-2025
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2025
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-025-06346-z
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Colon cancer illustration/© (M) KATERYNA KON / SCIENCE PHOTO LIBRARY / Getty Images