Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis
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 scre...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2015/230642 |
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| author | Jing Shen Shuang Wang Abby B. Siegel Helen Remotti Qiao Wang Iryna Sirosh Regina M. Santella |
| author_facet | Jing Shen Shuang Wang Abby B. Siegel Helen Remotti Qiao Wang Iryna Sirosh Regina M. Santella |
| author_sort | Jing Shen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-04656ebb991f4ec4a9e166c661e7a720 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-04656ebb991f4ec4a9e166c661e7a7202025-02-03T01:03:02ZengWileyGastroenterology Research and Practice1687-61211687-630X2015-01-01201510.1155/2015/230642230642Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in HepatocarcinogenesisJing Shen0Shuang Wang1Abby B. Siegel2Helen Remotti3Qiao Wang4Iryna Sirosh5Regina M. Santella6Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USADepartment of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USADepartment of Medicine, Columbia University Medical Center, New York, NY 10032, USADepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USABackground. 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.http://dx.doi.org/10.1155/2015/230642 |
| spellingShingle | Jing Shen Shuang Wang Abby B. Siegel Helen Remotti Qiao Wang Iryna Sirosh Regina M. Santella Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis Gastroenterology Research and Practice |
| title | Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis |
| title_full | Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis |
| title_fullStr | Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis |
| title_full_unstemmed | Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis |
| title_short | Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis |
| title_sort | genome wide expression of micrornas is regulated by dna methylation in hepatocarcinogenesis |
| url | http://dx.doi.org/10.1155/2015/230642 |
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