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Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis

Yang Zhang1,2, Wei Zhu1, Ruijie Tao2

  • 1Department of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.

Journal of Translational Medicine
|January 25, 2025
PubMed
Abstract

Insights

A novel peptide, Cathepsin B Derived Peptide 1 (CBDP1), shows promise in treating clear cell renal cell carcinoma (ccRCC). CBDP1 inhibits ccRCC progression by regulating the USP5/YTHDF2/TRPM3 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) presents a significant clinical challenge due to its high incidence, poor prognosis, and limited effective therapies.
  • Peptide-based therapeutics are emerging as a promising strategy for cancer treatment.
  • This study identifies and investigates a novel endogenous peptide, CBDP1, within ccRCC tissues for its potential anti-cancer activity.

Purpose of the Study:

  • To discover and characterize a novel endogenous peptide, CBDP1, in ccRCC.
  • To evaluate the anti-cancer effects of CBDP1 on ccRCC progression both in vitro and in vivo.
  • To elucidate the molecular mechanisms underlying CBDP1's antitumor activity.

Main Methods:

  • Peptidomics was employed to screen for potential antitumor peptides in ccRCC.
  • In vitro assays (Colony Formation, CCK-8, Transwell, Wound Healing) and in vivo animal models were used to assess CBDP1's impact on ccRCC growth and migration.
  • Molecular techniques including lentivirus transduction, Western Blot, qRT-PCR, Immunoprecipitation, Immunofluorescence, and Immunohistochemistry were utilized to investigate the antitumor mechanisms.

Main Results:

  • Cathepsin B Derived Peptide 1 (CBDP1) demonstrated significant inhibition of ccRCC progression in both in vitro and in vivo models.
  • CBDP1 was found to enhance the interaction between YTHDF2 and USP5, preventing YTHDF2 ubiquitination and degradation.
  • Upregulated YTHDF2 promotes TRPM3 mRNA degradation, leading to reduced TRPM3 expression and contributing to CBDP1's anti-cancer effects.

Conclusions:

  • CBDP1 exerts its antitumor effects in ccRCC by modulating the USP5/YTHDF2/TRPM3 signaling axis.
  • The findings highlight CBDP1 as a potential therapeutic candidate for ccRCC treatment.
  • Further research into CBDP1 could lead to novel therapeutic strategies for this challenging cancer.
Keywords:
Clear cell renal cell carcinomaEndogenous peptideTRPM3USP5YTHDF2

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