Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2016-08-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/8/8/76 |
| _version_ | 1797709807528968192 |
|---|---|
| author | Yuan Tian Myth T.S. Mok Pengyuan Yang Alfred S.L. Cheng |
| author_facet | Yuan Tian Myth T.S. Mok Pengyuan Yang Alfred S.L. Cheng |
| author_sort | Yuan Tian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:42:13Z |
| format | Article |
| id | doaj.art-5d52de57713e401ba912640008a3c013 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:42:13Z |
| publishDate | 2016-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5d52de57713e401ba912640008a3c0132023-09-03T00:54:36ZengMDPI AGCancers2072-66942016-08-01887610.3390/cancers8080076cancers8080076Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated HepatocarcinogenesisYuan Tian0Myth T.S. Mok1Pengyuan Yang2Alfred S.L. Cheng3Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaNon-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.http://www.mdpi.com/2072-6694/8/8/76non-alcoholic fatty liver diseasehepatocellular carcinomaWntβ-cateninepigeneticsDNA methylationhistone modificationmicroRNAHDAC8 |
| spellingShingle | Yuan Tian Myth T.S. Mok Pengyuan Yang Alfred S.L. Cheng Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis Cancers non-alcoholic fatty liver disease hepatocellular carcinoma Wnt β-catenin epigenetics DNA methylation histone modification microRNA HDAC8 |
| title | Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis |
| title_full | Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis |
| title_fullStr | Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis |
| title_full_unstemmed | Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis |
| title_short | Epigenetic Activation of Wnt/β-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis |
| title_sort | epigenetic activation of wnt β catenin signaling in nafld associated hepatocarcinogenesis |
| topic | non-alcoholic fatty liver disease hepatocellular carcinoma Wnt β-catenin epigenetics DNA methylation histone modification microRNA HDAC8 |
| url | http://www.mdpi.com/2072-6694/8/8/76 |
| work_keys_str_mv | AT yuantian epigeneticactivationofwntbcateninsignalinginnafldassociatedhepatocarcinogenesis AT mythtsmok epigeneticactivationofwntbcateninsignalinginnafldassociatedhepatocarcinogenesis AT pengyuanyang epigeneticactivationofwntbcateninsignalinginnafldassociatedhepatocarcinogenesis AT alfredslcheng epigeneticactivationofwntbcateninsignalinginnafldassociatedhepatocarcinogenesis |