Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis

Um, Tae Hee; Kim, Haeryoung; Oh, Bong Kyeong; Kim, Myoung Soo; Kim, Kyung Sik; Jung, Guhung; Park, Young Nyun

doi:10.1016/j.jhep.2010.08.021

Cited by 145 publications

(131 citation statements)

References 30 publications

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“…Compared to working on gene mutation, it is more realistic to regulate epigenetic changes. Um et al (2011) presented that DNA methyltransferase inhibitors, including 5-azacytidine and 5-aza-20-deoxycytidine, may help to eliminate DNA hypermethylation rate as an epigenetic therapy. A recent study investigated the relationship between a methyl-deficient diet and promoter methylation status of 164 genes which altered multiple vital processes including lipid and glucose metabolism, DNA damage and repair, apoptosis, the development of fibrosis, and liver tissue remodeling (Tryndyak et al 2011).…”

Section: Clinical Application Using Epigenetic Modificationsmentioning

confidence: 99%

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

Zhao

Qin

Zhao

et al. 2013

Tohoku J. Exp. Med.

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Section: Clinical Application Using Epigenetic Modificationsmentioning

confidence: 99%

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

Zhao

Qin

Zhao

et al. 2013

Tohoku J. Exp. Med.

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“…Interestingly, Zucman-Rossi et al [79] recently demonstrated that the loss of Axin1 function is not equivalent to gain-of-function of β-catenin, suggesting that Axin1 could also be participating in other pathways in HCC. APC mutations are very rare in HCC and promoter methylation has been reported to play an important role in its inactivation [80] .…”

Section: Gsk3β Ckiα Axin and Apcmentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/ β-catenin pathway for potential therapy of HCC. hepatocellular carcinoma anD the unmet meDical neeDSLiver cancer ranks the fifth most common cancer in men and the second leading cause of cancer-related death. In women, it is the seventh most frequent cancer and sixth leading cause of cancer death [1] . Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Men are three times more likely to develop HCC than women and the incidence increases with age [2] . HCC is prevalent in Asia and Africa, but recently it is on the rise in the Western world due to an increase in hepatitis C virus (HCV) infection [3] . Risk factors for HCC include chronic hepatitis B virus (HBV) and HCV infections, cirrhosis, chronic alcohol abuse, aflatoxin ingestion, non-alcoholic steatohepatitis and other metabolic liver diseases [4,5] . Much of HCC occurs in the background of cirrhosis. About 80%-90% of patients with cirrhosis go on to develop HCC eventually and the remaining 10%-20% of cases develop HCC without cirrhosis. Furthermore, HBV and HCV infections increase the risk of developing cirrhosis and later HCC. Among the HCC

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“…HCC development, similarly to that of other types of cancer, is a multistep process, involving numerous genetic and epigenetic alterations (3). It has been reported that promoter methylation of certain tumor suppressor genes occurs frequently during HCC development and progression (4,5).…”

Section: Introductionmentioning

confidence: 99%

Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

et al. 2015

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Abstract. GATA5 is a transcription factor that is capable of suppressing the development of various types of human cancer. The present study investigated the expression of GATA5 and GATA4, and examined their roles in the proliferation and colony formation ability of hepatocellular carcinoma (HCC) tissues and cells. The GATA4 and GATA5 expression levels and gene promoter methylation of HCC tissue samples from 38 patients and HCC cell lines were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP), respectively. The effects of GATA4 and GATA5 overexpression on the proliferation and colony forming ability of HCC cells were also assessed using cell viability and colony formation assays. A luciferase reporter assay was utilized to investigate the transcriptional interaction of GATA4 and GATA5 with canonical Wnt signaling. The results indicated that the expression levels of GATA4 and GATA5 were lost or reduced following methylation of gene promoters in HCC tissues and cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine (5-AZA), restored GATA4 and GATA5 expression in HCC cell lines. Furthermore, methylation of the GATA5 promoter was observed to be associated with the age of patients exhibiting HCC. Restoration of GATA4 and GATA5 expression inhibited colony formation and induced apoptosis of HCC cells in vitro. The present study concluded that the expression levels of GATA4 and GATA5 were reduced in HCC tissues and cell lines. Treatment with 5-AZA restored GATA4 and GATA5 expression in HCC cell lines, suppressing tumor cell growth and colony formation, as well as inducing apoptosis.

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Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis

Cited by 145 publications

References 30 publications

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

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