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GSE61286
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In order to propagate a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. To systematically identify genes that modulate cancer cell survival under stresses, we performed genome-wide shRNA screens under hypoxia or lactic acidosis. We discovered that genetic depletion of acetyl-CoA carboxylase (ACACA or ACC1) or ATP citrate lyase (ACLY) protected cancer cells from hypoxia-induced apoptosis. Additionally, loss of ACLY or ACC1 reduced levels and activities of the oncogenic transcription factor ETV4. Silencing ETV4 also protected cells from hypoxia-induced apoptosis and led to remarkably similar transcriptional responses as with silenced ACLY or ACC1, including an anti-apoptotic program. Metabolomic analysis found that while -ketoglutarate levels decrease under hypoxia in control cells, -ketoglutarate is paradoxically increased by hypoxia when ACC1 or ACLY are depleted. Supplementation with -ketoglutarate rescued the hypoxia-induced apoptosis and recapitulated the decreased expression and activity of ETV4 via an epigenetic mechanism. Therefore, ACC1 and ACLY regulate the levels of ETV4 under hypoxia via increased -ketoglutarate. These results reveal that ACC1/ACLY- -ketoglutarate-ETV4 is a novel means by which metabolic states regulate transcriptional output for life vs. death decisions under hypoxia. Since many lipogenic inhibitors are under investigation as cancer therapeutics, our findings suggest that the use of these inhibitors will need to be carefully considered with respect to oncogenic drivers, tumor hypoxia, progression and dormancy. More broadly, our screen provides a framework for studying additional tumor cell stress-adaption mechanisms in the future.
Publication Title
ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
NextSeq 500
Description
Purpose: We tested global gene transcriptome changes by RNA-sequencing analysis in the offspring breast tumors of SV40 transgenic mice to further identify key epigenetic-controlled genes in regulation of the prenatal/maternal BSp diet-mediated early breast cancer prevention. Method: Mouse offspring mammary tumor mRNA from control and maternal BSp treatment were generated by deep sequencing, in duplicate or triplicate, using Illumina NextSeq500 platform (GPL19057). The sequence reads that passed quality filters were analyzed. We utilized the R/Bioconductor package DESeq to evaluate differential gene expression for sequence count data by the use of negative binomial distributio. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: Our data showed differential transcriptome distribution in the breast tumors of mouse offspring between the control and prenatal/maternal BSp treatment groups. Overall design: Total RNA obtained from the offspring breast tumors of SV40 transgenic mice with mothers fed either control or BSp diets, and analyzed by Illumina NextSeq500 platform (GPL19057).
Publication Title
Temporal Efficacy of a Sulforaphane-Based Broccoli Sprout Diet in Prevention of Breast Cancer through Modulation of Epigenetic Mechanisms.
Sample Metadata Fields
Age, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
transcriptome profiling of miR-92a inhibitor treated and control cells with the aim of measuring miR-92a influence on its mRNA targets
Publication Title
Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cells transiently adapt to hypoxia by globally decreasing protein translation. However, specific proteins needed to respond to hypoxia evade this translational repression. The mechanisms of this phenomenon remain unclear. We screened for and identified small molecules that selectively decrease HIF-2a translation in an mTOR independent manner, by enhancing the binding of Iron Regulatory Protein 1 (IRP1) to a recently reported Iron-Responsive Element (IRE) within the 5-untranslated region (UTR) of the HIF-2a message. Knocking down the expression of IRP1 by shRNA abolished the effect of the compounds. Hypoxia de-represses HIF-2a translation by disrupting the IRP1- HIF-2a IRE interaction. Thus, this chemical genetic analysis describes a molecular mechanism by which translation of the HIF-2a message is maintained during conditions of cellular hypoxia through inhibition of IRP-1 dependent repression. It also provides the chemical tools for studying this phenomenon.
Publication Title
Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HESC-H9 and iPSC lines 3.5, 3.6 and 3.12 were analyzed using Affymetrix microarray before and after Definitive Endoderm (DE) formation. DE was induced using the ActivinA differentiation protocol described by D'Amour et al., 2006 (PMID: 16258519) Clustering analysis of transcripts that were differentially regulated during DE formation indicated that iPSC lines 3.5 and 3.12 differentiate in manner that is highly similar to HESC-H9 cells iPSC line 3.6 had a more divergent transcriptional profile.
Publication Title
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Three master regulatory transcription factors Pdx1, MafA and Ngn3 have the ability to transdifferentiate pancreatic acinar cells to insulin-producing beta cells in mice. BRD7552 was identified as a small-molecule inducer that can upregulate the expression of Pdx1 in PANC-1 cells by high-throughput qPCR screening.
Publication Title
A small-molecule inducer of PDX1 expression identified by high-throughput screening.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 52 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
We performed gene expression profiling of 26 colorectal tumors and matched histologically normal adjacent colonic tissue samples using the Illumina Ref-8 whole-genome expression BeadChip. We performed an integrated analysis of promoter DNA methylation and gene expression data to investigate the effects of DNA hypermethylation on gene expression.
Publication Title
Genome-scale analysis of aberrant DNA methylation in colorectal cancer.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6).
Publication Title
The intersection of genetic and chemical genomic screens identifies GSK-3α as a target in human acute myeloid leukemia.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood.
Publication Title
Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix CytoScan HD Array (cytoscanhdarray), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Subject
View Samples