Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The classic development of CRC is a process from normal colonic mucosa to polyp to eventually adenocarcinoma. However, the critical genes regulating this process and the underlying molecular mechanisms remain elusive. Here, we identified ZNF473 as an upregulated and key functional gene in CRC progression. Specifically, comprehensive bioinformatics analyses were performed to explore the expression of ZNF473 in CRC samples and to investigate its correlation with clinicopathological characteristics, prognosis, and potential biological functions. In vitro experiments were performed to elucidate the potential role and molecular mechanisms of ZNF473 in CRC progression. Results demonstrate that ZNF473 is highly expressed in CRC and correlates with poor prognosis. Functionally, ZNF473 knockdown significantly inhibits cell viability and proliferation. Furthermore, gene function enrichment analyses reveal an association between ZNF473 and pathways related to drug metabolism (Cytochrome P450) and chemotherapy resistance. Mechanistically, ZNF473 physically interact with p53 to promote its protein degradation, consequently upregulates the Survivin expression. In summary, this study reveals the role and molecular function of ZNF473 in CRC progression, uncovering a potential novel ZNF473/p53/Survivin axis and providing a hint for targeting ZNF473 to suppress tumor growth and potential chemoresistance.
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Funding
This work was supported by the Natural Science Foundation of Hunan Province, China (No. R2023JJ60368), Hunan Province Health High-level Talent Scientific Research Project (China) (No. R2023148), and Hunan Province Science Communication Research and Practice Project (China) (No. kxcbkt2025052).
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This study was approved by the Ethics Committee of the First Affiliated Hospital of USC (REC No. 2023LL0810002). The ethical guidelines in accordance with the Declaration of Helsinki. Written informed consent was obtained from all individual participants included in the study.
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Xu, Y., Fu, G., Fang, Q. et al. ZNF473 promotes colorectal cancer progression and chemoresistance by destabilizing p53 protein to upregulate Survivin. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03145-4
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DOI: https://doi.org/10.1038/s41420-026-03145-4
