Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis
Abstract Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC an...
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06091-4 |
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| author | Yang Zhang Wei Zhu Ruijie Tao Weijian Li Chunming Jiang Xiang Yan |
| author_facet | Yang Zhang Wei Zhu Ruijie Tao Weijian Li Chunming Jiang Xiang Yan |
| author_sort | Yang Zhang |
| collection | DOAJ |
| description | Abstract Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC and its potential anti-cancer properties were examined. Methods: Peptide expression in ccRCC was analyzed using peptidomics technology to screen for potential antitumor peptides. The effects of the peptide on ccRCC growth and migration were studied through Colony Formation Assay, CCK-8 assay, Transwell Assays, Wound Healing Assay, and animal experiments. Further investigation into the antitumor mechanisms of the peptide was conducted using lentivirus transduction, Western Blot Analysis, qRT-PCR, Immunoprecipitation, Immunofluorescence, and Immunohistochemistry. Results: Our findings reveal that Cathepsin B Derived Peptide 1 (CBDP1) can inhibit the progression of ccRCC both in vitro and in vivo. Through mechanistic investigations, it was revealed that CBDP1 facilitates the interaction between YTHDF2 and the deubiquitinase USP5, thereby impeding the ubiquitination and degradation of YTHDF2. The upregulated YTHDF2 then binds to TRPM3 mRNA and promotes its degradation, ultimately reducing TRPM3 expression levels. These molecular events collectively contribute to the anti-cancer properties of CBDP1. Conclusion: These data indicate that CBDP1 exerts its antitumor effects by regulating the USP5/YTHDF2/TRPM3 axis. CBDP1 emerges as a promising candidate for the treatment of ccRCC. |
| format | Article |
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| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-b3d97f6ea6bb43c48aa87ffa0694e8bd2025-01-26T12:50:19ZengBMCJournal of Translational Medicine1479-58762025-01-0123111810.1186/s12967-025-06091-4Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axisYang Zhang0Wei Zhu1Ruijie Tao2Weijian Li3Chunming Jiang4Xiang Yan5Department of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityMedical School of Nanjing UniversityDepartment of Urology, Northern Jiangsu People’s HospitalDepartment of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityMedical School of Nanjing UniversityAbstract Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC and its potential anti-cancer properties were examined. Methods: Peptide expression in ccRCC was analyzed using peptidomics technology to screen for potential antitumor peptides. The effects of the peptide on ccRCC growth and migration were studied through Colony Formation Assay, CCK-8 assay, Transwell Assays, Wound Healing Assay, and animal experiments. Further investigation into the antitumor mechanisms of the peptide was conducted using lentivirus transduction, Western Blot Analysis, qRT-PCR, Immunoprecipitation, Immunofluorescence, and Immunohistochemistry. Results: Our findings reveal that Cathepsin B Derived Peptide 1 (CBDP1) can inhibit the progression of ccRCC both in vitro and in vivo. Through mechanistic investigations, it was revealed that CBDP1 facilitates the interaction between YTHDF2 and the deubiquitinase USP5, thereby impeding the ubiquitination and degradation of YTHDF2. The upregulated YTHDF2 then binds to TRPM3 mRNA and promotes its degradation, ultimately reducing TRPM3 expression levels. These molecular events collectively contribute to the anti-cancer properties of CBDP1. Conclusion: These data indicate that CBDP1 exerts its antitumor effects by regulating the USP5/YTHDF2/TRPM3 axis. CBDP1 emerges as a promising candidate for the treatment of ccRCC.https://doi.org/10.1186/s12967-025-06091-4Clear cell renal cell carcinomaEndogenous peptideYTHDF2TRPM3USP5 |
| spellingShingle | Yang Zhang Wei Zhu Ruijie Tao Weijian Li Chunming Jiang Xiang Yan Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis Journal of Translational Medicine Clear cell renal cell carcinoma Endogenous peptide YTHDF2 TRPM3 USP5 |
| title | Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis |
| title_full | Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis |
| title_fullStr | Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis |
| title_full_unstemmed | Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis |
| title_short | Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis |
| title_sort | endogenous peptide cbdp1 inhibits clear cell renal cell carcinoma progression by targeting usp5 ythdf2 trpm5 axis |
| topic | Clear cell renal cell carcinoma Endogenous peptide YTHDF2 TRPM3 USP5 |
| url | https://doi.org/10.1186/s12967-025-06091-4 |
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