{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:07:47Z","timestamp":1770336467646,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TRIM16 has been identified as a tumor suppressor in hepatocellular carcinoma (HCC). This study aimed to investigate whether there are genetic variants in <jats:italic>TRIM16<\/jats:italic> influencing HCC risk and\/or prognosis and explore the mechanisms. We performed a gene\u2010wide single\u2010nucleotide polymorphism (SNP) mining in <jats:italic>TRIM16<\/jats:italic>. The associations of SNPs with both HCC risk and prognosis were assessed through two independent cohorts respectively. Functional experiments were performed to investigate the underlying mechanisms. A missense variant rs2074890 (G\u2009&gt;\u2009T, resulting in an amino acid substitution from glutamate to aspartate at code 121, E121D) of <jats:italic>TRIM16<\/jats:italic> was found to be associated with both HCC risk (odds ratio\u2009=\u20090.806, <jats:italic>p<\/jats:italic>\u2009=\u20090.023) and prognosis (hazard ratio\u2009=\u20090.44, <jats:italic>p<\/jats:italic>\u2009=\u20090.034). Compared to the rs2074890 G allele (corresponding to TRIM16<jats:sub>121E<\/jats:sub>) homozygote carriers, the rs2074890 T allele (corresponding to TRIM16<jats:sub>121D<\/jats:sub>) carriers showed lower HCC risk and better overall survival. Mechanistically, TRIM16<jats:sub>121D<\/jats:sub> has stronger ability to inhibit proliferation, migration, and invasion of HCC cells. Furthermore, TRIM16<jats:sub>121D<\/jats:sub> could bind to \u03b2\u2010catenin better and mediate K48\u2010linked ubiquitination to degrade \u03b2\u2010catenin, which leads to inhibition of Wnt\/\u03b2\u2010catenin pathway. In conclusion, <jats:italic>TRIM16<\/jats:italic> E121D variant impacts both risk and prognosis of HCC via regulation of Wnt\/\u03b2\u2010catenin pathway, which may lead to better understanding the pathogenesis of HCC.<\/jats:p>","DOI":"10.1002\/mc.23608","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T13:20:06Z","timestamp":1689945606000},"page":"1686-1699","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>TRIM16<\/i> E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt\/\u03b2\u2010catenin pathway"],"prefix":"10.1002","volume":"62","author":[{"given":"Shanfeng","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit Institutes of Liver Diseases Research of Guangdong Province, 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