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GSE6014
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a novel selective anticancer agent.
Publication Title
A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Publication Title
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 525 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. 28 CEBPAdouble-mut and 13 CEBPAsingle-mut cases. CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1 mutation, white blood cell count and age. In contrast, CEBPAsingle-mut AMLs did not express a discriminating signature and could not be distinguished from wild type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance.
Publication Title
Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Angiotensin II (Ang II)-mediated vascular smooth muscle cells (VSMC) dysfunction plays a critical role in cardiovascular diseases. However, the gene expression in this process is unclear.
Publication Title
Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Rattus norvegicus
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Angiotensin II (Ang II)-mediated vascular smooth muscle cells (VSMC) dysfunction plays a critical role in cardiovascular diseases. However, the role of microRNAs (miRNAs) in this process is unclear. We used small RNA deep sequencing to profile Ang II-regulated miRNAs in rat VSMC and evaluated their role in VSMC dysfunction. Sequencing results revealed several Ang II-responsive miRNAs and bioinformatics analysis showed that their predicted targets can modulate biological processes relevant to cardiovascular diseases. Overall design: Examined 4 samples of Rat VSMC. Control (without Ang II treatment) and 3 samples treated with Ang II for 1h, 3h, and 24h. Compared the changes in gene expression in Ang II treated samples relative to control samples.
Publication Title
Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Macrophage dysfunction and polarization plays key role in chronic inflammation associated with diabetes and its complications. However, the effect of diabetes on macrophage transcriptome including long non-coding RNAs is not known. Here, we analyzed global changes in transcriptome of bone marrow macrophages isolated from type 2 diabetic db/db mice and control littermates db/+ mice using high throughput RNA-seq technique. Data analysis showed that expression of genes relevant to fibrosis, cell adhesion and inflammation were altered in diabetic db/db mice relative to control db/+ mice. Furthermore, expression of several known and novel long non coding RNAs and nearby genes was altered in db/db mice. Gene ontology and IPA showed activation of signaling netwroks relevant to fibrosis, cell adhesion and inflammatory pathways . This study for the first time demonstrated that diabetes profoundly affects macrophage transcriptome including expression of long non coding RNAs and altered the levels of genes relevant to diabetes complications. Overall design: Bone marrow macrophages were isolated from 12 weeks old type 2 diabetic male db/db mice and control littermates db/+ mice. These were differentiated in culture for 7-8 days in the presence of 10 ng/ml of MCSF-1 (BMMC) or 20 ng/ml of GM-CSF (BMGM). Then RNA was extracted and used for RNA-seq.
Publication Title
Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- NextSeq 500
Description
Human dendritic cells were exposed to LPS, in the absence and presence of adenosine receptor 3 inhibitor Overall design: 4 donors, 4 experimental conditions. VUF concentration used was 5 µM, LPS was 500 ng/ml. Exposure times were 6 hours
Publication Title
TLR-Induced IL-12 and CCL2 Production by Myeloid Cells Is Dependent on Adenosine A<sub>3</sub> Receptor-Mediated Signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 210 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Left ventricular myocardium was snap-frozen at time of cardiac transplantation from patients with advanced idiopathic or ischemic cardiomyopathy, or at time of harvest from unused donor heart that serve as a nonfailing control. No subjects received mechanical support devices.
Publication Title
Transcriptional genomics associates FOX transcription factors with human heart failure.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 71 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntingtons disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation. We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics.
Publication Title
HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples