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A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Identification of a novel ferroptosis-inducing micropeptide in bladder cancer
Weijian Li1, Ye Shen2, Chen Yang1
1Department of Urology, Huashan Hospital, Fudan University, Shanghai, China; Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Abstract:
Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.
Insights
A novel peptide, CTSGDP-13, shows promise for treating bladder cancer (BC) by inducing ferroptosis. It targets TRIM25, offering new therapeutic avenues for this common male malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer (BC) presents significant therapeutic challenges, particularly in males.
- Endogenous peptides are emerging as potential therapeutic targets for improving BC prognosis.
Purpose of the Study:
- To identify and characterize novel endogenous peptides with anti-cancer effects in bladder cancer.
- To elucidate the molecular mechanisms underlying the anti-tumor activity of CTSGDP-13 in BC.
Main Methods:
- In vitro and in vivo studies were conducted to assess the anti-cancer effects of CTSGDP-13.
- Mechanistic investigations involved analyzing protein-protein interactions, ubiquitination, and degradation pathways.
- The USP7/TRIM25/KEAP1 axis was examined in relation to CTSGDP-13 activity.
Main Results:
- CTSGDGDP-13 was identified as a novel endogenous peptide with potent anti-cancer effects in BC.
- CTSGDGDP-13 promotes ferroptosis in BC cells, inhibiting tumor progression both in vitro and in vivo.
- TRIM25, upregulated in BC, was identified as a downstream target of CTSGDP-13; CTSGDP-13 promotes TRIM25 ubiquitination and degradation via the USP7/TRIM25/KEAP1 axis.
Conclusions:
- CTSGDGDP-13 demonstrates significant potential as a therapeutic agent for bladder cancer by inducing ferroptosis.
- Targeting the USP7/TRIM25/KEAP1 axis offers a promising strategy for BC treatment.
- Understanding the roles of CTSGDP-13 and TRIM25 provides valuable insights for BC diagnosis and therapy.
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