Details

Autor(en) / Beteiligte

• Udali, Silvia
• Guarini, Patrizia
• Ruzzenente, Andrea
• Ferrarini, Alberto
• Guglielmi, Alfredo
• Lotto, Valentina
• Tononi, Paola
• Pattini, Patrizia
• Moruzzi, Sara
• Campagnaro, Tommaso
• Conci, Simone
• Olivieri, Oliviero
• Corrocher, Roberto
• Delledonne, Massimo
• Choi, Sang-Woon
• Friso, Simonetta

Titel

DNA methylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma

Ist Teil von

• Clinical epigenetics, 2015-04, Vol.7 (1), p.43-43, Article 43

Ort / Verlag

Germany: BioMed Central Ltd

Erscheinungsjahr

2015

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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.