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Series GSE58232 Query DataSets for GSE58232
Status Public on Jul 07, 2014
Title Genome-wide analysis in Human Colorectal Cells reveals Ischaemia-mediated expression of motility genes via DNA hypomethylation (SNP array)
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary DNA hypomethylation is an important epigenetic modification found to occur in many different cancer types, leading to the upregulation of previously silenced genes and loss of genomic stability. We previously demonstrated that hypoxia and hypoglycaemia (ischemia), two common micro-environmental changes in solid tumors, decrease DNA methylation through the downregulation of DNMTs in human colorectal cancer cells. Here, we utilized a genome-wide cross-platform approach to identify genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity pathway analysis software revealed that a significant proportion of the genes hypomethylated and upregulated were involved in cellular movement, including PLAUR and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation of upregulated expression of cellular movement genes was performed with qPCR. The correlation between ischemia and metastasis is well established in cancer progression, but the molecular mechanisms responsible for this common observation have not been clearly identified. Our novel results suggest that hypoxia and hypoglycaemia may be driving changes in DNA methylation through downregulation of DNMTs. This is the first report to our knowledge that provides an explanation for the increased metastatic potential seen in ischemic cells; i.e. that ischemia could be driving DNA hypomethylation and increasing expression of cellular movement genes.
Overall design Genomic DNA from the Human Colorectal cancer Cell line HCT116 was hybridized in duplicate to Affymetrix Human SNP 6.0 arrays. CNVs were determined by comparison to 270 sample HAPMAP data.
Contributor(s) Skowronski K, Andrews J, Rodenhiser D, Coomber B
Citation(s) 25079072
Submission date Jun 04, 2014
Last update date Nov 27, 2018
Contact name Brenda Coomber
Organization name University of Guelph
Department Department of Biomedical Sciences
Lab Ontario Veterinary College
Street address 50 Stone Road
City Guelph
State/province Ontario
ZIP/Postal code N1G 2W1
Country Canada
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (2)
GSM1404391 HCT116_rep1
GSM1404392 HCT116_rep2
This SubSeries is part of SuperSeries:
GSE58233 Genome-wide analysis in Human Colorectal Cells reveals Ischaemia-mediated expression of motility genes via DNA hypomethylation
BioProject PRJNA251657

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE58232_RAW.tar 60.0 Mb (http)(custom) TAR (of CEL)
GSE58232_SNP_6_transposed_for_GEO_submission.txt.gz 28.5 Mb (ftp)(http) TXT
Processed data are available on Series record

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