Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array

Shin, So Hyun; Kim, Baek Hui; Jang, Ja June; Suh, Kyung Suk; Kang, Gyeong Hoon

doi:10.3346/jkms.2010.25.8.1152

Cited by 49 publications

(46 citation statements)

References 30 publications

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“…On the other hand, when suffering early overfeeding, the hypothalamic POMC promoter becomes hypermethylated (Plagemann et al, 2009). Neuropeptide Y (NPY), one of the main appetite-inducing factors, was one of the ten CpG sites that were hypermethylated in mucosa from colorectal cancer patients when compared to normal mucosa (Kim YH et al, 2011), and is also frequently hypermethylated in hepatocellular carcinoma tissue samples (Shin et al, 2010). In this sense, it is crucial to understand the epigenetic mechanisms involved in the regulation of these genes in the hypothalamus in response to different hormonal, dietary and environmental factors in order to understand physiological and pathological aspects of appetite regulation that could provide potential targets for the treatment of obesity.…”

Section: Hormonal and Neuropeptide Imbalancementioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

253

161

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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Section: Hormonal and Neuropeptide Imbalancementioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

253

161

View full text Add to dashboard Cite

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“…Indeed, abnormal DNA methylation of several TSGs, such as RASSF1A, CDKN2A, CRABP1, GSTP1, CHRNA3, DOK1, SFRP1, GAAD45a, and CDKN2B, is reported to be associated with HCC, and hypermethylation of specific genes, such as CHFR and SYK is detected in advanced stages of HCC (6). However, the number of reported methylation-target genes is far fewer for HCC than for colon cancer or gastric cancer (7). Therefore, further identification of remaining targets for methylation may clarify the specific molecular events involved in HCC progression, enabling the prevention, diagnosis, and treatment of HCC to be approached as potential clinical applications of DNA methylation signature at a molecular level.…”

Section: Introductionmentioning

confidence: 99%

Integrative Array-Based Approach Identifies MZB1 as a Frequently Methylated Putative Tumor Suppressor in Hepatocellular Carcinoma

Matsumura

Imoto

Kozaki

et al. 2012

Clinical Cancer Research

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Purpose: The aim of this study was the identification of novel tumor suppressor genes (TSG) silenced by DNA hypermethylation in hepatocellular carcinoma (HCC).Experimental Design: We conducted integrative array-based approach for genome-wide screening of methylation targets using a methylated DNA immunoprecipitation-CpG island microarray and expression array in three universal hepatoma cell lines and normal liver tissue. Through detailed expression and functional analyses using hepatoma cell lines and primary HCC samples, we isolated novel TSGs for HCC.Results: A total of 642 genes were identified as methylated in three hepatoma cell lines but unmethylated in normal liver tissue, whereas 204 genes on autosomes were identified as genes unexpressed but restored after treatment with 5-aza-2 0 -deoxycytidine in these cell lines and expressed in normal tissue. Through the integration of results of the two-array analyses and further validation analyses of expression and methylation status in 17 cell lines and 30 primary tumors of hepatoma, we identified MZB1, marginal zone B and B1 cellspecific protein, encoding an endoplasmic reticulum protein, as a putative TSG frequently methylated within its CpG island in hepatoma. Among 162 patients with primary HCC, silencing of MZB1 protein was significantly and independently associated with a worse outcome. Restoration of MZB1 expression in hepatoma cells reduced cell proliferation in vitro and in vivo through G 1 -arrest. Conclusions: These results suggest that methylation-mediated silencing of MZB1 expression leads to loss of its tumor-suppressive activity, which may be a factor in the hepatocarcinogenesis, and is a useful prognosticator in HCC.

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“…IRF-5 is a direct target of p53 (9) and displays some tumor suppressor properties as it can induce p21, Bak, Bax and caspase-8 genes (6,10). Downregulation of IRF-5 by hypermethylation has been reported in hepatocellular carcinoma and gastric cancer (11,12). In contrast, IRF-5 is upregulated in thyroid cancer where it contributes to cell proliferation and survival (13).…”

Section: Introductionmentioning

confidence: 99%

Constitutive expression of IRF-5 in HTLV-1-infected T cells

Ishikawa

Senba

Barnes

et al. 2015

International Journal of Oncology

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Abstract. Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive and fatal leukemia of T cells. Interferon regulatory factor (IRF)-5 plays a critical role in the induction of interferon genes in viral infected cells. We examined the specific mechanisms underlying the expression and regulation of IRF-5 in HTLV-1-infected T cells. IRF-5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV-1-infected T-cell lines but not in uninfected T-cell lines. IRF-5 was also upregulated in HTLV-1-infected T-cell lines at protein level. Nuclear IRF-5 expression was noted in ATL cells present in lymph nodes and skin lesions. IRF-5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated V3 promoter. Microarray analysis of IRF-5-expressing uninfected T cells demonstrated that IRF-5 induced the expression of tumor necrosis factor family cytokines. The results suggest that IRF-5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATL.

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Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array

Cited by 49 publications

References 30 publications

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Integrative Array-Based Approach Identifies MZB1 as a Frequently Methylated Putative Tumor Suppressor in Hepatocellular Carcinoma

Constitutive expression of IRF-5 in HTLV-1-infected T cells

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