Genome-wide analysis in Human Colorectal Cells reveals Ischaemia-mediated expression of motility genes via DNA hypomethylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Brenda Coomber
PROVIDER: E-GEOD-58233 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description: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. Genomic DNA from the Human Colorectal cancer Cell line HCT116 cultured normally or in hypoxic or Hypoglycaemic conditions was enriched using Methylated DNA Immunoprecipitation, Amplified using whole genome amplification, and hybridized in triplicate (for each treatment) to Affymetrix Human promoter 1.0R arrays arrays.
2014-07-07 | E-GEOD-58050 | biostudies-arrayexpress
Project description: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. 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.
2014-07-07 | E-GEOD-58232 | biostudies-arrayexpress
Project description: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. HCT116 cells were grown in either Hypoxic or Hypoglycaemic conditions, and compared to cells grown under normal conditions
2014-07-07 | E-GEOD-58049 | biostudies-arrayexpress
Project description:The application of chemical dispersants during marine oil spills can affect the community composition and activity of native marine microorganisms. Several studies have indicated that certain marine hydrocarbon-degrading bacteria, such as Marinobacter spp., can be inhibited by chemical dispersants, resulting in lower abundances and/or reduced hydrocarbon-biodegradation rates. In this respect, a major knowledge gap exists in understanding the mechanisms underlying these observed physiological effects. Here, we performed comparative proteomics of the Deepwater Horizon isolate Marinobacter sp. TT1 grown under different conditions that varied regarding the supplied carbon sources (pyruvate vs. n-hexadecane) and whether or not dispersant (Corexit EC9500A) was added, or that contained crude oil in the form of a water-accommodated fraction (WAF) or chemically-enhanced WAF (CEWAF). We characterized the proteins associated with alkane metabolism and alginate biosynthesis in strain TT1, report on its potential for aromatic hydrocarbon biodegradation and present a proposed metabolism of Corexit components as carbon substrates for the strain. Our findings implicate Corexit in affecting hydrocarbon metabolism, chemotactic motility, biofilm formation, and inducing solvent tolerance mechanisms like efflux pumps in strain TT1. This study provides novel insights into dispersant impacts on microbial hydrocarbon degraders that should be taken into consideration for future oil spill response actions.
2020-12-22 | PXD021108 | Pride
Project description:HCT116 parental, HCT116 5-FU resistant and HCT116 oxaliplatin resistant cells have been transiently treated with with their respective drug (5-FU or oxaliplatin) for 0, 6 12 or 24h in 3 independent experiments.
2006-01-01 | E-MEXP-390 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of HCT116 WT, HCT116 DNMT1 and DNMT3B double KO, and breast cancer tumors by next generation Infinium assay Bisulfite converted DNA from 22 samples were hybridized to the Illumina's HumanMethylation450 BeadChip
2011-12-15 | E-GEOD-29290 | biostudies-arrayexpress
Project description:Study the effect of recombinant human FSH supplementation in the in vitro maturation medium for an incubation of 6 hrs on the transcriptomics of bovine cumulus cells. 3 biological replicates of cumulus cells derived from cumulus oocyte complexes (COCs) supplemented with FSH (CC-FSH) vs. cumulus cells without FSH (Ct-6H, REFERENCE) were contrasted. Each replicate was subjected to a dye-swap procedure.
2015-07-01 | E-GEOD-67970 | biostudies-arrayexpress
Project description:Immune cells need to swiftly and effectively respond to invading pathogens. This response relies heavily on rapid protein synthesis and accurate cellular targeting to ensure pathogen destruction. In return, pathogens intercept this response so they can survive and proliferate. To gain insight into this dynamic interface, we combined click-chemistry with pulsed stable isotope labelling of amino acids (pSILAC-AHA) and quantified the newly synthesised host proteome during macrophage infection with the model intracellular bacterial pathogen, Salmonella enterica Typhimurium (STm). We monitored newly synthesized proteins across different compartments and during different infection stages, and used available proteomics data in response to LPS to deconvolute the STm-specific response. Within this rich resource, we detect aberrant trafficking of lysosomal proteases to the extracellular space and the nucleus, the latter of which correlates with signatures of cell death. Pharmacological cathepsin inhibition suppressed caspase-11 dependent macrophage cell death, thus demonstrating an active role for cathepsins during STm induced pyroptosis. Our study illustrates the utility of resolving the host proteome dynamics during infection to drive the discovery of novel biological mechanisms at the host-microbe interface.
2020-01-24 | PXD010179 | Pride
Project description:Study the effect of forskolin, dipyridamol and IBMX (here called FID) supplementation in the in vitro maturation medium for an incubation of 6 hrs on the transcriptomics of bovine cumulus cells. 3 biological replicates of cumulus cells derived from cumulus oocyte complexes (COCs) supplemented with FID (CC-FID) vs. cumulus cells without FID (Ct-6H, REFERENCE) were contrasted. Each replicate was subjected to a dye-swap procedure.
2015-07-01 | E-GEOD-67968 | biostudies-arrayexpress
Project description:This sample was prepared with a modified version of the Tn4001 transposon commonly used in Mycoplasmas. This transposon is described to work more efficiently in Mycoplasma agalactiae and, by extension, in other Mycoplasma species. This sample was prepared transforming this bacteria with a newly designed transposon named pMTnGm-SynMyco to test its efficiency by Transposon Sequencing tracked by deep sequencing.
2019-11-15 | E-MTAB-7425 | biostudies-arrayexpress