Microarrays were used to detail the global programme of gene expression comparing wild-type and RNAi knock-down plants of SPT4-1 and SPT4-2
The transcript elongation factor SPT4/SPT5 is involved in auxin-related gene expression in Arabidopsis.
Age, Specimen part
View SamplesMutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, though, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on upregulation of the transcription factor ZEB1 and downregulation of the mir-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis
Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT).
Cell line
View SamplesThe catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma - a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein - display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers. Overall design: Three different in vivo models of synovial sarcoma (xenograft: Fuji; PDX: CTG-0331 and CTG-0771) treated with or without the indicated dose of the EZH2 inhibitor, tazemetostat
Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.
Subject
View SamplesPrevious study has shown that alpha1ACT is a transcription factor involved with regulating neuronal gene expression. We performed a time-series RNA-seq study using pc12 cell lines stably expressing pcDNA3-alpha1ACT at 4 time points (6hr, 24hr, 3day, and 10day) to explore the transcriptional profiles that capture transient and prolonged dynamic changes regulated by alpha1ACT during cell cycle and differentiation Overall design: PC12 cell lines expressing pcDNA3 (EV) and expressing pcDNA3-a1ACT at 4 different time points (6h, 24h, 3d, 10d) were analyzed by Agilent Bio-analyzer and submitted to university of Chicago Functional genomic facility for library preparation (TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold, RS-122-2301) and sequencing on Illumina HiSeq2500 platform, with 3 biological replicates for each condition.
α1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window.
Specimen part, Cell line, Subject, Time
View SamplesPanel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines
Interleukin 32 expression in human melanoma.
Disease, Disease stage, Cell line, Subject
View SamplesGene expression profile in circulating leukocytes identifies patients with coronary artery disease
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.
Sex, Age, Specimen part, Race
View SamplesWe performed RNA-seq analysis of polA transcripts in IMR-32 cells with shRNA-mediated depletion of CDK12 and CDK13 and GFP as a control Overall design: Expression of polA transcripts in IMR-32 cells with shRNA-mediated depletion of CDK12 and CDK13 using the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen) using 2 different shRNA constructs for each target in duplicate, for a total of 10 individual samples Please note that processed data files were generated from the merged replicates, as indicated in the corresponding sample description field.
CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation.
Specimen part, Cell line, Treatment, Subject
View SamplesWe performed RNA-seq analsysis of polA transcripts in Kelly and Kelly E9 resistant (E9R) cells treated with THZ531 for 6h and DMSO as a control Overall design: Expression of polA transcripts in Kelly and Kelly E9R cells treated with THZ531 using the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen) in duplicate, for a total of 8 indyvidual samples Please note that the bigWig processed data was generated from both replicates and is linked to the corresponding rep1 (*_1) sample records.
CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation.
Specimen part, Cell line, Treatment, Subject
View SamplesWe performed RNA-seq analsysis of polA transcripts in IMR-32 cells treated with THZ531 for 2 and 6h and DMSO as a control Overall design: Expression of polA transcripts in IMR-32 treated with THZ531 using the RNA-seq library kit (QuantSeq 3' mRNA Sequencing REV, Lexogen) in duplicate, for a total of 6 individual samples
CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation.
Cell line, Treatment, Subject
View SamplesWe used microarrays to compare the global programme of gene expression in HTLV-positive, ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells.
Elevated cyclic AMP levels in T lymphocytes transformed by human T-cell lymphotropic virus type 1.
Specimen part
View Samples