2. Academic Validation
  3. TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/β-catenin pathway

TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/β-catenin pathway

  • Mol Carcinog. 2023 Jul 21. doi: 10.1002/mc.23608.
Shanfeng Li 1 2 3,  Jialin Wang 1 4,  Haitao Chen 1 5,  Jia Hou 1,  Ting Shen 1,  Jing Li 1,  Bin Zhou 1,  Bo Zhang 4,  Hui Liu 6,  De-Ke Jiang 1 2
Affiliations

Affiliations

  • 1 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, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 The Key Laboratory of Molecular Pathology (Hepatic Diseases) of Guangxi, Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
  • 3 Department of Nosocomial Infection Management, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
  • 4 Guangdong-Hongkong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Public Health, Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 5 Department of Epidemiology, School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China.
  • 6 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
PMID: 37477507 DOI: 10.1002/mc.23608
Abstract

TRIM16 has been identified as a tumor suppressor in hepatocellular carcinoma (HCC). This study aimed to investigate whether there are genetic variants in TRIM16 influencing HCC risk and/or prognosis and explore the mechanisms. We performed a gene-wide single-nucleotide polymorphism (SNP) mining in TRIM16. 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 > T, resulting in an amino acid substitution from glutamate to aspartate at code 121, E121D) of TRIM16 was found to be associated with both HCC risk (odds ratio = 0.806, p = 0.023) and prognosis (hazard ratio = 0.44, p = 0.034). Compared to the rs2074890 G allele (corresponding to TRIM16121E ) homozygote carriers, the rs2074890 T allele (corresponding to TRIM16121D ) carriers showed lower HCC risk and better overall survival. Mechanistically, TRIM16121D has stronger ability to inhibit proliferation, migration, and invasion of HCC cells. Furthermore, TRIM16121D could bind to β-catenin better and mediate K48-linked ubiquitination to degrade β-catenin, which leads to inhibition of Wnt/β-catenin pathway. In conclusion, TRIM16 E121D variant impacts both risk and prognosis of HCC via regulation of Wnt/β-catenin pathway, which may lead to better understanding the pathogenesis of HCC.

Keywords

hepatocellular carcinoma; single-nucleotide polymorphism; tripartite motif 16; tumor prognosis; ubiquitination.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19987
    99.95%, Wnt Signaling Activator
    Wnt