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

Clinical Epigenetics

Simonetta Friso²  Sang-Woon Choi⁴  Massimo Delledonne¹  Roberto Corrocher²  Oliviero Olivieri²  Simone Conci³  Tommaso Campagnaro³  Sara Moruzzi²  Patrizia Pattini²  Paola Tononi¹  Valentina Lotto²  Alfredo Guglielmi³  Alberto Ferrarini¹  Andrea Ruzzenente³  Patrizia Guarini²  Silvia Udali² 

[1] Department of Biotechnology, Genetics and Heredity Section, University of Verona School of Agroindustrial Biotechnology, Ca’ Vignal 1, Strada Le Grazie 15, Verona, 37134, Italy;Department of Medicine, University of Verona School of Medicine, Policlinico ‘G.B. Rossi’, P.le L.A. Scuro, 10, Verona, 37134, Italy;Department of Surgery, University of Verona School of Medicine, Policlinico ‘G.B. Rossi’, P.le L.A. Scuro, 10, Verona, 37134, Italy;Chaum Life Center, CHA University, 4-1, Cheongdam-dong, Gangnam-gu, Seoul, 135-948, Korea

关键词: Retinol metabolism;    One-carbon metabolism;    MeDIP-chip;    Hepatocellular carcinoma;    Gene expression array;    Epigenetics;    DNA methylation;    Candidate tumor-suppressor genes;    Alcohol;   

Others  :  1210211
DOI  :  10.1186/s13148-015-0077-1

 received in 2015-03-23, accepted in 2015-03-26,  发布年份 2015

【 摘 要 】

Background

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.

Results

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).

Conclusions

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.

【 授权许可】

   
2015 Udali et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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