1. Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis.
- Author
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Yuan Tian, Mok, Myth T. S., Pengyuan Yang, and Cheng, Alfred S. L.
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HEPATOCELLULAR carcinoma , *ASIANS , *CELLULAR signal transduction , *PEOPLE with diabetes , *FATTY liver , *GENE expression , *GROWTH factors , *HISTONES , *LIVER , *GENETIC mutation , *OBESITY , *RNA , *METABOLIC syndrome , *DNA methylation , *EPIGENOMICS , *THERAPEUTICS - Abstract
Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/β-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/β-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding β-catenin protein) or other antagonists targeting Wnt/β-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal β-catenin activities in HCC. Emerging evidence has demonstrated that obesity-induced metabolic pathways can deregulate chromatin modifiers such as histone deacetylase 8 to trigger undesired global epigenetic changes, thereby modifying gene expression program which contributes to oncogenic signaling. This review focuses on the aberrant epigenetic activation of Wnt/ β-catenin in the development of NAFLD-associated HCC. A deeper understanding of the molecular mechanisms underlying such deregulation may shed light on the identification of novel druggable epigenetic targets for the prevention and/or treatment of HCC in obese and diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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