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Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis

Authors :
Iryna Sirosh
Abby B. Siegel
Jing Shen
Qiao Wang
Shuang Wang
Regina M. Santella
Helen Remotti
Source :
Gastroenterology Research and Practice, Vol 2015 (2015), Gastroenterology Research and Practice
Publication Year :
2015
Publisher :
Hindawi Limited, 2015.

Abstract

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

Details

Language :
English
ISSN :
16876121
Volume :
2015
Database :
OpenAIRE
Journal :
Gastroenterology Research and Practice
Accession number :
edsair.doi.dedup.....1bd0bf198deb166fdc9c0783666733a2