Research on the mechanism by which USP18 promotes colorectal cancer progression through stabilizing KRT16 expression

Background This study aims to investigate the effects of Ubiquitin-specific peptidase 18 (USP18) and Keratin16 (KRT16) on the progression of colorectal cancer and their possible mechanism of action. Methods The downstream target protein of USP18 was identified using Co-immunoprecipitation(Co-IP) and mass spectrometry. The clinical significance of KRT16 was validated via bioinformatics analysis of the TCGA database. Immunohistochemical staining detected USP18 and KRT16 expression in CRC tissues, and their relationship with clinicopathological features was analyzed. In vitro functional assays, including Western Blot, scratch tests, and CCK-8 assays, were performed using USP18 overexpression and KRT16 interference plasmids. Results KRT16 was identified as a downstream target of USP18, and USP18 overexpression was shown to deubiquitinate KRT16. Bioinformatics analysis revealed that KRT16 was highly expressed in CRC (P < 0.001), exhibited significant prognostic value (log-rank P = 0.029) and high diagnostic accuracy (AUC = 0.899). A positive correlation was found between KRT16 and USP18 expression (R = 0.308, P < 0.001). Immunohistochemistry confirmed that both KRT16 and USP18 were significantly upregulated in CRC tissues, with KRT16 expression correlating with T stage (P = 0.008). In vitro, KRT16 knockdown inhibited CRC cell proliferation and migration. Importantly, USP18 overexpression enhanced proliferation and migration, which was rescued by KRT16 knockdown. Conclusion KRT16 can be used as one of the markers of colorectal cancer, and USP18 may be involved in the occurrence and development of colorectal cancer by regulating the expression of KRT16.