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

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.