Hypomethylation of the c-myc oncogene in liver cirrhosis and chronic hepatitis

Aiba, Nobuyasu; Nambu, Shuji; Inoue, Katsumi; Sasaki, Hiroshi

doi:10.1007/bf02774324

Cited by 14 publications

(7 citation statements)

References 26 publications

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“…A previous report indicated the strong link between cirrhosis, HCC and the gene modification and methylation state of c-MYC in human liver tissue. In fact, hypomethylation of the c-MYC gene has been linked with liver cancer development [96], indicating that the state of DNA methylation can be used as a diagnostic tool for chronic liver damage.…”

Section: C-myc: Causing Liver Stiffnessmentioning

confidence: 99%

c-MYC—Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and Disease

Zheng

Cubero

Nevzorova

2017

Genes

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Over 35 years ago, c-MYC, a highly pleiotropic transcription factor that regulates hepatic cell function, was identified. In recent years, a considerable increment in the number of publications has significantly shifted the way that the c-MYC function is perceived. Overexpression of c-MYC alters a wide range of roles including cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion and differentiation. The purpose of this review is to broaden the understanding of the general functions of c-MYC, to focus on c-MYC-driven pathogenesis in the liver, explain its mode of action under basal conditions and during disease, and discuss efforts to target c-MYC as a plausible therapy for liver disease.

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Section: C-myc: Causing Liver Stiffnessmentioning

confidence: 99%

c-MYC—Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and Disease

Zheng

Cubero

Nevzorova

2017

Genes

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“…In order to metastasize, it is required that particular genetic programs should be expressed to activate appropriate interactions with varying microenvironments so as to improve continued survival and proliferation at secondary sites 7 – 9 . To understand the complex process of metastasis, it is necessary to figure out these genetic programs and the way they affect cellular interactions and signaling cascades 10 – 12 . Due to the complexity and heterogeneity of HCC, the molecular mechanism underlying its metastasis has not been completely unlocked yet 13 – 15 .…”

Section: Introductionmentioning

confidence: 99%

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

Lin

Huang

Liu

et al. 2018

Sci Rep

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Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.

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“…Our study revealed that RAS genes might be involved in the progression of HCC, in particular, NRAS . Different studies showed the overexpression of HRAS , KRAS, and NRAS in HCC. RAS and downstream RAS effectors are found to be activated in case of HCC due to the epigenetic silencing of the pathway inhibitor genes .…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have also been conducted on the methylation status of HRAS and KRAS oncogenes in HCC. In a study carried out in Japanese population, the CCGG sites of KRAS was found to be hypomethylated only in the tissue of patients with HCC in comparison to other non‐HCC chronic liver diseases and normal samples . The methylation pattern of KRAS was studied by Kaneko et al in human fetal liver and HCC in comparison of normal liver samples.…”

Section: Discussionmentioning

confidence: 99%

Study of promoter hypomethylation profiles of RAS oncogenes in hepatocellular carcinoma derived from hepatitis C virus genotype 3a in Pakistani population

Maryam

Idrees

2018

Journal of Medical Virology

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Epigenetic modifications such as DNA methylation contribute to progression of hepatitis C virus (HCV) infection to life-threatening hepatocellular carcinoma (HCC) by promoting the silencing of tumor suppressor genes through DNA hypermethylation and by causing genomic instability through global hypomethylation. However few studies have addressed the promoter region hypomethylation status of the oncogenes involved in HCV derived HCC. In this study, we analyzed the promoter region methylation pattern of RAS oncogenes (HRAS, KRAS, and NRAS) using methylation-specific PCR for 50 chronic HCV patients infected with genotype 3a (27 HCC patients and 23 control non-HCC patients). Methylation-specific polymerase chain reaction analysis revealed that the NRAS oncogene promoter (P = .0025) was significantly hypomethylated in HCC patients compared to the non-HCC patients suggesting its contribution to the progression of HCV towards HCC. To identify the agent for alteration in the RAS oncogene expression, 7 HCV genes were expressed in the Huh-7 cell line followed by measurement of the NRAS expression level in Huh-7 by a quantitative real-time polymerase chain reaction. An increase in the messenger RNA level of the NRAS gene was detected when Huh-7 were transfected with Core, NS5a, and NS2 genes. Our findings suggest the involvement of NRAS oncogene in the pathogenesis of HCV3a derived HCC in Pakistani population and also identifies the HCV genes responsible for its enhanced expression. Our study raises the hypothesis that a single HCV gene may increase the chances of malignancy. Therefore, our study may have identified a useful epigenetic biomarker of HCC progression in HCV patients and may help to develop novel diagnostic tools.

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Hypomethylation of the c-myc oncogene in liver cirrhosis and chronic hepatitis

Cited by 14 publications

References 26 publications

c-MYC—Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and Disease

c-MYC—Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and Disease

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

Study of promoter hypomethylation profiles of RAS oncogenes in hepatocellular carcinoma derived from hepatitis C virus genotype 3a in Pakistani population

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