1. Academic Validation
  2. GCNT3 regulated MUC13 to promote the development of hepatocellular carcinoma through the GSK3β/β-catenin pathway

GCNT3 regulated MUC13 to promote the development of hepatocellular carcinoma through the GSK3β/β-catenin pathway

  • Dig Liver Dis. 2024 Feb 17:S1590-8658(24)00246-9. doi: 10.1016/j.dld.2024.01.198.
Qiu Kang 1 Wu Tingting 2 Dong Bingzi 3 Zou Hao 1 Xie Yuwei 1 Sun Chuandong 4 Zhu Chengzhan 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266003, China.
  • 2 Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, China.
  • 3 Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266003, China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266003, China. Electronic address: suncd@qduhospital.cn.
  • 5 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266003, China. Electronic address: zhuchengz@qduhospital.cn.
Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Extensive research is currently directed at identifying novel targets for its diagnosis and treatment.

Aims: We investigated the biological functions and clinical significance of mucin-type N-acetylglucosaminyltransferase 3 (GCNT3) in HCC.

Methods: Variations in the mRNA expression of GCNT3 were examined in normal and HCC tissues. Cell function assays and animal models characterized the effects of GCNT3 on the proliferation, invasion, and migration abilities of HCC cells. Western blot and immunofluorescence analyses were performed to explore further the specific mechanisms whereby GCNT3 affects HCC progression.

Results: There is a strong correlation between GCNT3 overexpression and tumor formation and metastasis in vivo and in vitro. GCNT3 acted as a regulator of the synthesis of mucin-type O-glycans by interacting with Mucin 13 (MUC13) to regulate its expression levels, activating the GSK3β/β-catenin signaling pathway. The activation of GSK3β/β-catenin signaling by GCNT3 was mitigated by MUC13 knockdown. In clinical HCC specimens, GCNT3 expression was upregulated in HCC tissues compared to non-tumor tissues. Further, there was a significant correlation between high GCNT3 expression and poor patient survival.

Conclusions: GCNT3 regulated tumor progression in HCC through the MUC13/GSK3-β/β-catenin signaling pathway.

Keywords

GCNT3; Hepatocellular carcinoma; MUC13; Tumor metastasis; Tumor proliferation.

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