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Updated: May 17, 2025
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Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
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HBV core protein enhances WDR46 stabilization to upregulate NUSAP1 and promote HCC progression
Fanyun Kong1, Ensi Bao1, Yujie Zhong1
1Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Hepatology Communications
|May 14, 2025
Summary
Hepatocellular carcinoma (HCC) progression is linked to Hepatitis B virus core protein (HBC). HBC upregulates WD repeat-containing protein 46 (WDR46), promoting HCC by stabilizing WDR46 and increasing NUSAP1 expression.
Area of Science:
- Hepatology
- Oncology
- Molecular Biology
Background:
- Hepatitis B virus core protein (HBC) is a known driver of hepatocellular carcinoma (HCC).
- WD repeat-containing protein 46 (WDR46) is implicated in various cancers, but its role in HBC-driven HCC is not fully understood.
Purpose of the Study:
- To investigate the role of WDR46 in HBC-mediated hepatocarcinogenesis.
- To elucidate the molecular mechanisms by which HBC influences WDR46 and its downstream targets in HCC.
Main Methods:
- Analysis of HCC cohorts and bioinformatics.
- Immunohistochemistry, Western blotting, and co-immunoprecipitation.
- Functional assays to assess cell growth, migration, and protein stabilization.
Main Results:
- WDR46 expression is elevated in HBV-associated HCC in an HBC-dependent manner.
- HBC stabilizes WDR46 by inhibiting its ubiquitination via TRIM25, promoting HCC cell growth and migration.
- HBC-induced WDR46 upregulates NUSAP1 transcription via c-Myc recruitment to the NUSAP1 promoter.
Conclusions:
- WDR46 plays a critical role in HBC-induced hepatocarcinogenesis.
- WDR46 and its downstream target NUSAP1 represent potential therapeutic targets for HBV-related HCC.
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