Filters
Technology
Platform
GSE84992
Homo sapiens
30 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
To define the direct gene expression changes in normal human skeletal muscle with mineralocorticoid and glucocorticoid receptor agonist and antagonist treatment.
Publication Title
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
To uncover whether aldosterone induces gene expression changes through mineralocorticoid or glucocorticoid receptors and determine if eplerenone and spironolactone could block aldosterone induced gene expression to the same extent
Publication Title
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
To test for a function effect of mineralocorticoid receptor modulation in skeletal muscle, global gene expression analysis was conducted on human myltubes treated with a mineralocorticoid receptor agonist or antagonist.
Publication Title
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify the gene expression differences in skeletal muscles resulting from treatment of dystrophic mice with spironolactone plus lisinopril
Publication Title
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
NextSeq 500
Description
The Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Publication Title
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 147 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed and paraffin-embedded (FFPE) biopsies has many unique challenges. Here we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers from diagnostic prostate needle core biopsies.
Publication Title
Application of a Clinical Whole-Transcriptome Assay for Staging and Prognosis of Prostate Cancer Diagnosed in Needle Core Biopsy Specimens.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
The study demontrates differences in the transcriptome ( both of protein coding transcripts and long non-coding RNAs) in the unilateral ureteric obstruction model of renal fibrosis. Overall design: Renal tissue was studied from animals undergoing sham operation (as controls) or right ureteric ligation. Animals were sacrificed 2 and 8 days following ligation and the right kidney tissue was examined.
Publication Title
Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Screening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Publication Title
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
The transcriptional regulator EVI1 has an essential role in early hematopoiesis and development. However, aberrantly high expression of EVI1 has potent oncogenic properties and confers poor prognosis and chemo-resistance in leukemia and solid tumors. To investigate to what extent EVI1 function might be regulated by posttranslational modifications, we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. In the presence of genotoxic stress, EVI1-WT (SQS), but not site mutated EVI1-AQA was able to maintain transcriptional patterns and transformation potency, while under standard conditions carboxy-terminal mutation had no effect. Maintenance of hematopoietic progenitor cell clonogenic potential was profoundly impaired with EVI1-AQA compared with EVI1-WT, in particular in the presence of genotoxic stress. Exploring mechanistic events underlying these observations, we showed that after genotoxic stress EVI1-WT, but not EVI1-AQA increased its level of association with its functionally essential interaction partner CtBP1, implying a role for ATM in regulating EVI1 protein interactions via phosphorylation. This aspect of EVI1 regulation is therapeutically relevant, as chemotherapy-induced genotoxicity might detrimentally sustain EVI1 function via stress response mediated phosphorylation, and ATM-inhibition might be of specific targeted benefit in EVI1-overexpressing malignancies. Overall design: Poly-A RNA sequencing (RNAseq) analysis of EVI1-mediated modulation of gene expression RNA was extracted from HEK293 cells, which were subjected to transient transfection using half confluent cultures with pCMV-flag, pCMV-EVI1-WT-flag or pCMV-EVI1-AQA-flag, exposed to 150 µM H2O2 or left untreated for 8 h.
Publication Title
EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains transcriptional modulation and self-renewal via enhanced CtBP1 association.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples