PRDM15 promotes colorectal carcinogenesis by transcriptionally repressing USP10 to destabilize p53

PRDM15, a member of the PRDM family, is critically involved in embryonic development, cell differentiation, and tumorigenesis. However, its specific regulatory mechanisms in tumorigenesis remain poorly understood. This study demonstrates that PRDM15 is significantly upregulated in colorectal cancer (CRC) tissues and positively correlates with advanced pathological staging. Knockdown of PRDM15 inhibits p53-dependent cell proliferation by arresting cell cycle progression and promoting apoptosis, thereby suppressing colorectal carcinogenesis both in vitro and in vivo. Furthermore, PRDM15 depletion enhances the sensitivity of HCT116 cells to the chemotherapeutic agent 5-Fluorouracil (5-FU). Mechanistically, PRDM15 functions as a novel negative regulator of p53, exerting its oncogenic effects by transcriptionally downregulating USP10, which in turn destabilizes p53. These findings underscore the critical role of the PRDM15-USP10-p53 axis in CRC progression, offering new insights into the molecular mechanisms driving CRC and identifying potential therapeutic targets for intervention.