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GSE63036
Homo sapiens
4 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb- and p53-binding protein, is a component of this complex and functions in 3' processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (domain with no name), that is required for 3' processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 3' processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 3' untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 3' processing, especially of RNAs with AU-rich 3' UTRs.
Publication Title
RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3' UTRs.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The tumor suppressor TP53 is mutated in the majority of human cancers, including over 70% of pancreatic ductal adenocarcinoma (PDAC). Wild-type p53 accumulates in response to cellular stress and regulates the expression of genes that alter cell fate and constrain tumorigenesis. p53 also modulates several cellular metabolic pathways, though it remains unclear whether particular p53-regulated metabolites contribute to tumor suppression or whether metabolic alterations driven by p53 mutation sustain cancer progression. Here, we show that restoring endogenous p53 function in cancer cells derived from a murine PDAC model driven by oncogenic Kras and a regulatable p53 short hairpin RNA (shRNA) rewires glucose and glutamine metabolism leading to the accumulation of a-ketoglutarate (aKG), an obligate substrate for several chromatin modifying enzymes. p53 induces transcriptional programs characteristic of premalignant differentiation, an effect that can be partially recapitulated by addition of cell permeable aKG. Similarly, enforcing aKG accumulation in p53-deficient PDAC cells though the inhibition of oxoglutarate (aKG) dehydrogenase (Ogdh), the enzyme that consumes aKG in the tricarboxylic acid cycle, reduces tumor-initiating capacity and promotes tumor cell differentiation. Decreases in 5-hydroxymethylcytosine (5hmC), an aKG-dependent chromatin modification, are associated with the appearance of p53 mutations in the transition from premalignant to de-differentiated malignant lesions, whereas increases in 5hmC accompany tumor cell differentiation triggered by either p53 restoration or Ogdh depletion. Together these data nominate aKG as an effector of p53-mediated tumor suppression whose accumulation in p53-deficient tumors can drive tumor cell differentiation and antagonize malignant progression. Overall design: 6 samples were analyzed in duplicates of 3 conditions. 1. Control, KPsh cells grown on dox, treated with vehicle DMSO for 72 hours. 2. KPsh cells grown on dox, treated with 4mM cell permeable dimethyl-alpha ketoglutarate for 72 hours. 3. KPsh cells grown off dox for 8 days, treated with DMSO vehicle for 72 hours.
Publication Title
α-Ketoglutarate links p53 to cell fate during tumour suppression.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer can be divided in two major histological subtypes: diffuse and intestinal-type adenocarcinomas. Since both types diverge in many clinical and molecular characteristics, is widely accepted that both represent distinct disease entities that may benefit from different therapeutic approaches. The diffuse type is explicitly more invasive and affected patients possess extremely poor prognosis. Gene expression profiling studies identified numerous genes with differences in mRNA expression between the two types. However, little overlap of published gene lists exists forcing the need for further and more comprehensive analyses.
Publication Title
THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Schizosaccharomyces pombe
- 3 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
An branched-chain amino acids auxotroph eca39 mutant fission yeast exhibits an unusual adaptive growth phenotype on solid minimal media containing Ile, Leu and Val when other strains are growing nearby.
Publication Title
The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tcf1 is necessary for optimal T lineage development. Tcf1 deficient progenitors fail to initiate the T lineage program in vitro and development is severely defective in vivo. We used microarrays to assess the overal global gene expression differences from Tcf1 wildtype and deficient lymphoid biased progenitors cultures on Notch-ligand expressing stroma to determine if Tcf1 deficient progenitors are able to intiate the T lineage specification program.
Publication Title
A critical role for TCF-1 in T-lineage specification and differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to perform a global gene expression analysis in Tcf1-expressing Thy1+CD25+ T lineage cells that develop on OP9 stroma in the absence of Notch1 signals. We compare this to the starting population, LMPP progenitors, and to control expressing T lineage cells that developed on OP9 stroma expressing Notch ligand DL4. The overall goal of this study was to determine if Tcf1 initiates T lineage specification in lymphoid progenitors. We found that Tcf1 was sufficient to upregulate many T lineage genes as compared to control expressing progenitors on OP9-DL4.
Publication Title
A critical role for TCF-1 in T-lineage specification and differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The differences of clinical characteristics in complex seizures induced by influenza A(H1N1)pdm09 and rotavirus gastroenteritis are well known, but the pathogenic mechanisms remain unclear. We analyzed the gene expression profiles in the peripheral whole blood cells isolated from pediatric patients using an Affymetrix oligonucleotide microarray.
Publication Title
Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of LPS-stimulated bone marrow-derived dendritic cells with NR4A3 gene silencing
Publication Title
The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tankyrase enhances beta-catenin signaling via PARsylation and subsequent degradation of Axin, a negative regulator of beta-catenin. Tankyrase inhibitors stabilize Axin and suppress beta-catenin signaling. We developed a novel tankyrase inhibitor, RK-287107.
Publication Title
RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Publication Title
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Sample Metadata Fields
Cell line
View Samples