Emerging role of zinc finger protein A20 as a suppressor of hepatocellular carcinoma

J Cell Physiol. 2019 Dec;234(12):21479-21484. doi: 10.1002/jcp.28877. Epub 2019 May 27.

Abstract

Hepatocellular carcinoma (HCC), the third leading cause of cancer-associated mortality worldwide, is a major public health problem. Zinc finger protein A20 (A20), an acute phase response gene, is a potent inhibitor of NF-κB signaling. A20 serves a critical role in liver protection, including limiting inflammation following hepatic injury, stimulating hepatocyte growth, and preventing hepatic ischemia-reperfusion injury. A20 is also involved in different processes, including tumorigenesis, progression, and metastasis through multiple mechanisms. Accumulated studies have reported the clinical implications and biological relevance of A20 in the development and progression of HCC. The underlying mechanisms of A20 in HCC include inhibition of epithelial-mesenchymal transition, protein tyrosine kinase 2 activation and Rac family GTPase 1 activity. Combining liver protection with tumor inhibition is a unique advantage of A20, which has the potential to be a novel treatment for promoting liver regeneration following liver resection in patients with HCC with liver cirrhosis. This review discusses the hepato-protective effect of A20 on hepatocytes and its potential role in cancer development, particularly its suppressor effect on HCC.

Keywords: hepatectomy; hepatocellular carcinoma; liver regeneration; suppressor; zinc finger protein A20.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Epithelial-Mesenchymal Transition / physiology
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Liver Regeneration / physiology
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism*

Substances

  • Tumor Necrosis Factor alpha-Induced Protein 3