Effects of Sirt1 manipulation on gene expression in human Caco-2 cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30486 | GEO | 2012/07/05
SECONDARY ACCESSION(S): PRJNA143479
REPOSITORIES: GEO
Similar Datasets
Project description:To compare gene expression in human intestinal cell line after Sirt1 manipulation by overexpression or targetted siRNA knockdown Triplicate biological replicates for Caco-2 control and Sirt1 overexpression (6 samples), duplicate biological replicates for Caco-2 control siRNA and two non-overlapping targetted Sirt1 siRNAs (6 samples)
2012-07-04 | E-GEOD-30486 | biostudies-arrayexpress
Project description:Beneficial effects of SIRT1 on healthspan are likely to be pleiotropic and may include effects on DNA methylation. We demonstrated recently that manipulating SIRT1 in human cells affected DNA methylation of a panel of test genes, and that genes with expression modified by dietary restriction corresponded with genes that underwent changes in DNA methylation during ageing. Here we tested the hypothesis that genes particularly susceptible to SIRT1-induced effects on DNA methylation across the genome map to genes for which DNA methylation changes during ageing. We increased or reduced SIRT1 expression in human intestinal (Caco-2) and vascular endothelial (HuVEC) cells by transient transfection with an expression construct or with siRNA, respectively. Effects on DNA methylation were measured by enriching for the methylated fraction then either sequencing (HuVEC) or hybridising to a human promoter microarray (Caco-2). Effects using these two different cell lines and techniques for analysis were remarkably consistent. Genes with a DNA methylation status affected by SIRT1 manipulation were enriched for those that undergo age-dependent changes in DNA methylation, thus supporting our hypothesis. Polycomb group protein target genes (PCGTs), which are suppressed by epigenetic mechanisms in stem cells and have been shown previously to correspond with loci particularly susceptible to age-related changes in DNA methylation, were over-represented within the set of genes showing altered DNA methylation in response to SIRT1 manipulation in both cell lines. We thus propose that effects of SIRT1 to extend healthspan include influences on the DNA methylation status of genes affected during ageing, in particular PCGTs. Analysis of methylation profiles of Caco-2 cells meeting the following conditions: SIRT1 overexpressed by transfection with pCMV6-ENTRY-SIRT1 (2 replicates), corresponding vector control (2 replicates), each of the siRNAs that target SIRT1 (1 & 2 replicates, respectively) and control siRNA (2 replicates).
2014-03-31 | E-GEOD-53569 | biostudies-arrayexpress
Project description:Beneficial effects of SIRT1 on healthspan are likely to be pleiotropic and may include effects on DNA methylation. We demonstrated recently that manipulating SIRT1 in human cells affected DNA methylation of a panel of test genes, and that genes with expression modified by dietary restriction corresponded with genes that underwent changes in DNA methylation during ageing. Here we tested the hypothesis that genes particularly susceptible to SIRT1-induced effects on DNA methylation across the genome map to genes for which DNA methylation changes during ageing. We increased or reduced SIRT1 expression in human intestinal (Caco-2) and vascular endothelial (HuVEC) cells by transient transfection with an expression construct or with siRNA respectively. Effects on DNA methylation were measured by enriching for the methylated faction then either sequencing (HuVEC) or hybridising to a human promoter microarray (Caco-2). Effects using these two different cell lines and techniques for analysis were remarkably consistent. Genes with a DNA methylation status affected by SIRT1 manipulation were enriched for those that undergo age-dependent changes in DNA methylation, thus supporting our hypothesis. Polycomb group protein target genes (PCGTs), which are suppressed by epigenetic mechanisms in stem cells and have been shown previously to correspond with loci particularly susceptible to age-related changes in DNA methylation, were over-represented within the set of genes showing altered DNA methylation in response to SIRT1 manipulation in both cell lines. We thus propose that effects of SIRT1 to extend healthspan include influences on the DNA methylation status of genes affected during ageing, in particular PCGTs. MBD-Sequencing to ascertain effects of SIRT1 over & under expression on methylation, in presence and absence of TNF-alpha. One sample per condition.
2014-06-30 | E-GEOD-54072 | biostudies-arrayexpress
Project description:Beneficial effects of SIRT1 on healthspan are likely to be pleiotropic and may include effects on DNA methylation. We demonstrated recently that manipulating SIRT1 in human cells affected DNA methylation of a panel of test genes, and that genes with expression modified by dietary restriction corresponded with genes that underwent changes in DNA methylation during ageing. Here we tested the hypothesis that genes particularly susceptible to SIRT1-induced effects on DNA methylation across the genome map to genes for which DNA methylation changes during ageing. We increased or reduced SIRT1 expression in human intestinal (Caco-2) and vascular endothelial (HuVEC) cells by transient transfection with an expression construct or with siRNA respectively. Effects on DNA methylation were measured by enriching for the methylated faction then either sequencing (HuVEC) or hybridising to a human promoter microarray (Caco-2). Effects using these two different cell lines and techniques for analysis were remarkably consistent. Genes with a DNA methylation status affected by SIRT1 manipulation were enriched for those that undergo age-dependent changes in DNA methylation, thus supporting our hypothesis. Polycomb group protein target genes (PCGTs), which are suppressed by epigenetic mechanisms in stem cells and have been shown previously to correspond with loci particularly susceptible to age-related changes in DNA methylation, were over-represented within the set of genes showing altered DNA methylation in response to SIRT1 manipulation in both cell lines. We thus propose that effects of SIRT1 to extend healthspan include influences on the DNA methylation status of genes affected during ageing, in particular PCGTs.
2014-06-30 | GSE54072 | GEO
Project description:Beneficial effects of SIRT1 on healthspan are likely to be pleiotropic and may include effects on DNA methylation. We demonstrated recently that manipulating SIRT1 in human cells affected DNA methylation of a panel of test genes, and that genes with expression modified by dietary restriction corresponded with genes that underwent changes in DNA methylation during ageing. Here we tested the hypothesis that genes particularly susceptible to SIRT1-induced effects on DNA methylation across the genome map to genes for which DNA methylation changes during ageing. We increased or reduced SIRT1 expression in human intestinal (Caco-2) and vascular endothelial (HuVEC) cells by transient transfection with an expression construct or with siRNA, respectively. Effects on DNA methylation were measured by enriching for the methylated fraction then either sequencing (HuVEC) or hybridising to a human promoter microarray (Caco-2). Effects using these two different cell lines and techniques for analysis were remarkably consistent. Genes with a DNA methylation status affected by SIRT1 manipulation were enriched for those that undergo age-dependent changes in DNA methylation, thus supporting our hypothesis. Polycomb group protein target genes (PCGTs), which are suppressed by epigenetic mechanisms in stem cells and have been shown previously to correspond with loci particularly susceptible to age-related changes in DNA methylation, were over-represented within the set of genes showing altered DNA methylation in response to SIRT1 manipulation in both cell lines. We thus propose that effects of SIRT1 to extend healthspan include influences on the DNA methylation status of genes affected during ageing, in particular PCGTs.
2014-03-31 | GSE53569 | GEO
Project description:The goal of this project is to investigate the role of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, in the regulation of intestinal tissue integrity. Using a mouse model with specific deletion of SIRT1 in intestinal epithelium (SIRT1 iKO mice), we recently discovered that deletion of intestinal SIRT1 in mice age-dependently elicits NF-κB signaling and other stress response pathways, activates intestinal secretory cells, enhances spontaneous inflammation, and alters commensal gut microbial composition. To understand the molecular mechanisms underlying these age-dependent phenotypes, we examined the transcriptomes of young (6-8 week old) and aged (24-month old) ilea and aged colons from Flox controls and SIRT1 iKO mice by microarray analysis.
2017-05-30 | GSE86475 | GEO
Project description:To investigate the specific roles of SIRT1 in the development of hepatocellular carcinoma, we employed large-scale gene expression analysis to identify the molecular signature that may affect enabling characteristics of cancer cells. Differentially expressed genes were analyzed on the SNU-182 cells transfected with SIRT1 siRNA and recapitulated molecular signatures that related to hallmarks of cancer. SIRT1 expression in hepatocellular carcinoma was analyzed by RT-PCR and western blot. RNA interference-mediated protein knockdown method was used to investigate oncogenic potential of SIRT1 in hepatocelluar carcinoma
2012-03-01 | E-GEOD-32066 | biostudies-arrayexpress
Project description:To investigate the specific roles of SIRT1 in the development of hepatocellular carcinoma, we employed large-scale gene expression analysis to identify the molecular signature that may affect enabling characteristics of cancer cells. Differentially expressed genes were analyzed on the SNU-182 cells transfected with SIRT1 siRNA and recapitulated molecular signatures that related to hallmarks of cancer.
2012-03-01 | GSE32066 | GEO
Project description:The goal of this project is to understand the dosage-dependent effects of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, on cell proliferation and metabolism. Our recent studies indicate that SIRT1 has a dosage-dependent effect on cell metabolism and proliferation. Heterozygous deletion of SIRT1 enhance glycolysis and glutaminolysis, thereby promoting cell proliferation and stress resistance. Yet homozygous deletion of SIRT1 triggers cellular apoptotic pathways, leading to increased cell death. To understand the molecular mechanisms underlying this dose-dependent effect, we examined the transcriptomes of SIRT1 WT, Het, and KO MEFs cultured in complete DMEM medium by microarray analysis.
2016-12-20 | GSE76088 | GEO
Project description:Pancreatic cancer is a common malignant tumor with poor prognosis. Accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers.SIRT1 plays an important role in tumorigenesis, development, and drug resistance by blocking aging and apoptosis, also promoting cell growth and angiogenesis.However, how SIRT1 functions in the development of pancreatic cancer stem cells (CSCs) is currently poorly understood. Here, we showed that SIRT1 is involved in regulating various pathways closely related to tumor growth, autophagy and stemness, as well as promoting pancreatic CSC development.
2021-06-18 | GSE171118 | GEO