DNA methylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma.
DNA methylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma.
复制标题
DOI：
10.1186/s13148-015-0077-1
复制
发表时间：
2015
影响因子：
5.7
通讯作者：
Friso S
中科院分区：
文献类型：
--
作者：
Udali S;Guarini P;Ruzzenente A;Ferrarini A;Guglielmi A;Lotto V;Tononi P;Pattini P;Moruzzi S;Campagnaro T;Conci S;Olivieri O;Corrocher R;Delledonne M;Choi SW;Friso S
酒精是众所周知的肝细胞癌（HCC）危险因素，但与酒精相关的肝癌发生的机制仍知之甚少。酒精会改变肝脏一碳代谢中甲基的供应，可能诱导异常的 DNA 甲基化。然而，在酒精相关的 HCC 中，特定途径是否受到表观遗传调控尚不清楚。本研究的目的是研究非病毒性酒精相关性 HCC 中的全基因组启动子 DNA 甲基化和基因表达谱。通过比较 HCC 组织和同源的无癌肝组织，分析了 8 名接受根治性手术的 HCC 患者的所有注释基因的基于芯片的 DNA 甲基化和基因表达数据。将 DNA 甲基化与基因表达数据合并后，我们鉴定了 159 个高甲基化抑制基因、30 个低甲基化诱导基因、49 个高甲基化诱导基因和 56 个低甲基化抑制基因。值得注意的是，启动子 DNA 甲基化作为一种新的转录抑制机制出现，用于控制视黄醇代谢（ADH1A、ADH1B、ADH6、CYP3A43、CYP4A22、RDH16）、铁稳态（HAMP）、一碳代谢（SHMT1）的基因以及具有假定的、新发现的肿瘤抑制基因（FAM107A、IGFALS、MT1G、 MT1H、RNF180）。全基因组 DNA 甲基化方法与基于芯片的基因表达谱相结合，可以在酒精相关肝癌发生中鉴定出许多新颖的、表观遗传调控的候选肿瘤抑制基因。在酒精相关的 HCC 中，视黄醇代谢基因和 SHMT1 也通过启动子 DNA 甲基化受到表观遗传调控。由于环境/营养因素影响表观遗传机制的可逆性，这些发现可能为预防与酒精（一种可改变的饮食成分）相关的肝癌相关的肝癌发生开辟新的干预策略。本文的在线版本 (doi:10.1186/s13148-015-0077-1) 包含补充材料，可供授权用户使用。
Alcohol is a well-known risk factor for hepatocellular carcinoma (HCC), but the mechanisms underlying the alcohol-related hepatocarcinogenesis are still poorly understood. Alcohol alters the provision of methyl groups within the hepatic one-carbon metabolism, possibly inducing aberrant DNA methylation. Whether specific pathways are epigenetically regulated in alcohol-associated HCC is, however, unknown. The aim of the present study was to investigate the genome-wide promoter DNA methylation and gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients undergoing curative surgery, array-based DNA methylation and gene expression data of all annotated genes were analyzed by comparing HCC tissue and homologous cancer-free liver tissue. After merging the DNA methylation with gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced, and 56 hypomethylated-repressed genes. Notably, promoter DNA methylation emerged as a novel regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolism (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16), iron homeostasis (HAMP), one-carbon metabolism (SHMT1), and genes with a putative, newly identified function as tumor suppressors (FAM107A, IGFALS, MT1G, MT1H, RNF180). A genome-wide DNA methylation approach merged with array-based gene expression profiles allowed identifying a number of novel, epigenetically regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically regulated through promoter DNA methylation in alcohol-associated HCC. Due to the reversibility of epigenetic mechanisms by environmental/nutritional factors, these findings may open up to novel interventional strategies for hepatocarcinogenesis prevention in HCC related to alcohol, a modifiable dietary component. The online version of this article (doi:10.1186/s13148-015-0077-1) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.2
作者：
Friso, S;Choi, SW
通讯作者：
Choi, SW
影响因子：
7
作者：
Feber, Andrew;Wilson, Gareth A.;Beck, Stephan
通讯作者：
Beck, Stephan
DOI：
10.1073/pnas.062066299
发表时间：
2002-04-16
影响因子：
11.1
作者：
Friso, S;Choi, SW;Selhub, J
通讯作者：
Selhub, J
DOI：
10.1007/978-1-60327-414-2_15
发表时间：
2009-01-01
期刊：
CHROMATIN IMMUNOPRECIPITATION ASSAYS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Goval, Jean-Jacques;Magdalena, Juana
通讯作者：
Magdalena, Juana
影响因子：
4
作者：
Friso, Simonetta;Lotto, Valentina;Olivieri, Oliviero
通讯作者：
Olivieri, Oliviero