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GSE22865
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Extracellular, cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology.
Publication Title
Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Long non coding RNAs are implemented in epigenetic changes and regulation of gene expression. HOTAIR is a promising lncRNA concerning epigenetic regulation. We performed HOTAIR overexpression and knockdown experiments in mesenchymal stromal cells derived from bone marrow. After two weeks cells were harvested and RNA and DNA were isolated. Analysis of gene expression was performed with Human Gene 2.0 ST Array (Affymetrix, Santa Clara, USA). Analysis of DNA methylation was performed with Infinium HumanMethylation450 BeadChips (Illumina, San Diego, USA)
Publication Title
The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene expression signatures were measured after treatment of cells with 50nM BEZ235. Affymetrix HG-U133AV2 expression arrays were performed according to the manufacturer's directions using RNA extracted by Qiagen RNeasy from engineered human cell-lines grown for 72h in the presence of 50nM BEZ235
Publication Title
PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth.
Publication Title
Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Illumina HiSeq 1500
Description
The epithelial-mesenchymal transition (EMT) is a multistep dedifferentiation program important in tissue repair. Here, we examined the role of the transcriptional regulator NFkB in EMT of human primary small airway epithelial cells (hSAECs). Surprisingly, transforming growth factor ß (TGFß) activated NFkB/RELA proto-oncogene, NFkB subunit (RELA) translocation within 1 day of stimulation, yet induction of its downstream gene regulatory network occurred only after 3 days. A time course of TGFß-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFß stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified Wnt, cadherin, and NFkB signaling as the most prominent TGFß-inducible pathways. By comparison, RELA controlled expression of 3,138 overlapping genes mapping to Wnt, cadherin, and chemokine signaling pathways. Conducting upstream regulator analysis, we found that RELA controls six clusters of upstream transcription factors, many of which overlapped with a transcription factor topology map of EMT developed earlier. RELA triggered expression of three key EMT pathways: (1) the Wnt/ß-catenin morphogen pathway, (2) the JUN transcription factor, and (3) the Snail family transcriptional repressor 1 (SNAI1). RELA binding to target genes was confirmed by ChIP. Experiments independently validating Wnt dependence on RELA were performed by silencing RELA via genome editing and indicated that TGFß-induced WNT5B expression and downstream activation of the Wnt target AXIN2 are RELA-dependent. We conclude that RELA is a master transcriptional regulator of EMT upstream of Wnt morphogen, JUN, SNAI1-ZEB1, and interleukin-6 autocrine loops. Overall design: RNA-seq transcriptome profiling of TGF-Beta stimulated RelA wildtype and knock-down cells
Publication Title
The NFκB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In somatic cells elevated temperature induces activation of the heat shock transcription factor 1 (HSF1) what leads to heat shock proteins synthesis and cytoprotection. However, in the male germ cells (spermatocytes) upon HSF1 activation, caspase-3 dependent apoptosis is induced and spermatogenic cells are actively eliminated.
Publication Title
Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We were interested to explain why p53 binds some high affinity sites in contrast to other high affinity sites that are not bound by p53.
Publication Title
p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy.
Sample Metadata Fields
Cell line, Treatment
View Samples