2. Academic Validation
  3. Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression

Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression

  • Cell Death Discov. 2024 Aug 6;10(1):352. doi: 10.1038/s41420-024-02122-z.
Hui Zhang 1 2,  Xiameng Su 2,  Leirong Gu 2,  Ming Tan 2,  Yuting Liu 2,  Kexin Xu 2,  Jihua Ren 2,  Juan Chen 2 3,  Zhihong Li 2,  Shengtao Cheng 4 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
  • 3 The State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, P. R. China.
  • 4 Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. shengtao@cqmu.edu.cn.
  • 5 The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China. shengtao@cqmu.edu.cn.
PMID: 39107264 DOI: 10.1038/s41420-024-02122-z
Abstract

The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for Antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti-HBc compound-colchicine, an alkaloid compound-that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective Autophagy of HBc by enhancing the binding of HBc to the Autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

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