Identification of radiation-induced aberrant hypomethylation in colon cancerReport as inadecuate




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BMC Genomics

, 16:56

First Online: 06 February 2015Received: 06 September 2014Accepted: 09 January 2015DOI: 10.1186-s12864-015-1229-6

Cite this article as: Bae, JH., Kim, JG., Heo, K. et al. BMC Genomics 2015 16: 56. doi:10.1186-s12864-015-1229-6

Abstract

BackgroundExposure to ionizing radiation IR results in the simultaneous activation or downregulation of multiple signaling pathways that play critical roles in cell type-specific control of survival or death. IR is a well-known genotoxic agent and human carcinogen that induces cellular damage through direct and indirect mechanisms. However, its impact on epigenetic mechanisms has not been elucidated, and more specifically, little information is available regarding genome-wide DNA methylation changes in cancer cells after IR exposure. Recently, genome-wide DNA methylation profiling technology using the Illumina HumanMethylation450K platform has emerged that allows us to query >450,000 loci within the genome. This improved technology is capable of identifying genome-wide DNA methylation changes in CpG islands and other CpG island-associated regions.

ResultsIn this study, we employed this technology to test the hypothesis that exposure to IR not only induces differential DNA methylation patterns at a genome-wide level, but also results in locus- and gene-specific DNA methylation changes. We screened for differential DNA methylation changes in colorectal cancer cells after IR exposure with 2 and 5 Gy. Twenty-nine genes showed radiation-induced hypomethylation in colon cancer cells, and of those, seven genes showed a corresponding increase in gene expression by reverse transcriptase polymerase chain reaction RT-PCR. In addition, we performed chromatin immunoprecipitation ChIP to confirm that the DNA-methyltransferase 1 DNMT1 level associated with the promoter regions of these genes correlated with their methylation level and gene expression changes. Finally, we used a gene ontology GO database to show that a handful of hypomethylated genes induced by IR are associated with a variety of biological pathways related to cancer.

ConclusionWe identified alterations in global DNA methylation patterns and hypomethylation at specific cancer-related genes following IR exposure, which suggests that radiation exposure plays a critical role in conferring epigenetic alterations in cancer.

KeywordsIonizing radiation 5-aza-2′-deoxycytidine DNA hypomethylation Methylation profiling Gene ontology Colon cancer Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1229-6 contains supplementary material, which is available to authorized users.

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Author: Jin-Han Bae - Joong-Gook Kim - Kyu Heo - Kwangmo Yang - Tae-Oh Kim - Joo Mi Yi

Source: https://link.springer.com/



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