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SRP094652
Homo sapiens
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Solid tumors are less oxygenated than normal tissues, and for this reason the cancer cells have developed several molecular mechanisms of adaptation to hypoxic environment. Moreover, his poor oxygenation is a major indicator of an adverse prognosis and leads resistance to standard anticancer treatment. Previous reports from this laboratory showed an involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions, and on the basis of these observations, we hypothesized that Che-1 might have a role in the response of cancer cells to hypoxia. Methods: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA, was subjected to normoxic and hypoxic conditions to perform studies about the role of this protein in metabolic adaptation and cell proliferation. The expression of Che-1 under normoxia or hypoxia was detected using western blot assays; cell metabolism was assessed by NMR spectroscopy and functional assays. Further molecular studies were performed by RNA seq, qRT-PCR and ChIP analysis. Results: In this paper we report that Che-1 expression is required for the adaptation of the cells to hypoxia, playing and important role in metabolic modulation. Indeed, Che-1 depletion impacted on glycolysis by altering the expression of several genes involved in the response to hypoxia by modulating the levels of HIF-1alpha. Conclusions: These data demonstrate a novel player in the regulation of a HIF1alpha in response to hypoxia. We found that the transcriptional down-regulation of a members of E3 ubiquitin ligase family SIAH2 by Che-1, produces a failure in the degradation by the hydroxylase PHD3 with a decrease in HIF-1alpha levels during hypoxia. Overall design: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA was profiled for mRNA high-troughput sequencing (RNA-seq)
Publication Title
Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
To elucidated through an unbiased manner which genes and pathways are differentially regulated during mouse colonic inflammation followed by a tissue regeneration phase. In particular, we took advantage of the widely used dextran sodium sulfate (DSS)-induced model of colitis. This model is one of the few characterized by a phase of damage followed by a phase of regeneration. Therefore, this model gave the possibility to identify also sets of genes essential in the regeneration phase, a key step towards the resolution of the inflammation. In short, mice were exposed to DSS in the drinking water for 7 days, then allowed to recover for the following 7 days. During this period, we collected colonic tissue samples every second day to then be analyzed by RNA sequencing (RNA-seq). Next, we performed a RNA-seq analysis from colonic samples throughout the experiment and computed differentially expressed genes (DEGs) taking the complete kinetics of expression into consideration for p-value estimation using EdgeR. Overall design: C57BL/6J female mice were treated with 2.5% DSS in order to induce colinic inflammation. 2-3 animals were sacrificed at different time points when the colonic tissue was collected.
Publication Title
Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Publication Title
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Che-1 is a RNA Polymerase II binding protein involved in the regulation of gene transcription. We have observed that Che-1 depletion induces apoptosis in several cancer cells expressing mutated forms of p53. We used microarrays to investigate classes of genes regulated by Che-1 in one of these cell lines.
Publication Title
Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Full title: Expression data from human primary subcutaneous preadipocytes treated with glucocorticoids prior to the initiation of differentiation.
Publication Title
Insulin sensitization of human preadipocytes through glucocorticoid hormone induction of forkhead transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify targets of PDGFRb signaling and potentially new markers for pericyte activation, we used microarray analysis to compare gene expression in control and mutant pericytes expressing a constitutively active PDGFRb.
Publication Title
PDGFRβ signaling regulates mural cell plasticity and inhibits fat development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
PDGF and FGF treatment in E13.5 MEPMs. 4 hr PDGF treated MEPMs (3 replicates), 4 hr FGF treated MEPMs (3 replicates), 1 hr PDGF + PD325901 treated MEPMs (2 replicates), 4 hr PDGF + PD325901 treated MEPMs (2 replicates), 1 hr FGF + PD325901 treated MEPMs (2 replicates), 4 hr FGF + PD325901 treated MEPMs (2 replicates), 1 hr PDGF + LY294002 treated MEPMs (2 replicates), 4 hr PDGF + LY294002 treated MEPMs (2 replicates), 1 hr FGF + LY294002 treated MEPMs (2 replicates), 4 hr FGF + LY294002 treated MEPMs (2 replicates) Overall design: 4 hr PDGF treated MEPMs (3 replicates), 4 hr FGF treated MEPMs (3 replicates), 1 hr PDGF + PD325901 treated MEPMs (2 replicates), 4 hr PDGF + PD325901 treated MEPMs (2 replicates), 1 hr FGF + PD325901 treated MEPMs (2 replicates), 4 hr FGF + PD325901 treated MEPMs (2 replicates), 1 hr PDGF + LY294002 treated MEPMs (2 replicates), 4 hr PDGF + LY294002 treated MEPMs (2 replicates), 1 hr FGF + LY294002 treated MEPMs (2 replicates), 4 hr FGF + LY294002 treated MEPMs (2 replicates)
Publication Title
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Receptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that SRF is induced by both PDGF and FGF signaling in mouse embryonic palatal mesenchyme cells, and Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a novel role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a unique PDGF-responsive SRF-driven transcriptional program in the midface. Overall design: Serum Starved MEPMs (4 replicates), 1 hr PDGF treated MEPMs (4 replicates), 1 hr FGF treated MEPMs (3 replicates)
Publication Title
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 200 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006.
Publication Title
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. Overall design: Vehicle vs. ReACp53 treatment in 4 different samples: 2 cell lines (MCF7 w/ WT p53 as negative control and OVCAR3 w/ R248Q p53) and 2 clinical specimens (primary cells from patient #8 w/ WT p53 as negative control and primary cells from patient #1 w/ R248Q p53)
Publication Title
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas.
Sample Metadata Fields
No sample metadata fields
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