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GSE39612
Homo sapiens
132 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCC, may drive tumorigenesis via viral T antigens. However, mechanisms underlying pathogenesis in MCPyV-negative MCC remain poorly understood. To nominate genes contributing to pathogenesis of MCPyV-negative MCC, we performed DNA microarray analysis on 30 MCCs. MCPyV status of MCCs was determined by PCR for viral DNA and RNA. 1593 probe-sets were differentially expressed between MCPyV-negative and -positive MCC, with significant differential expression defined as at least 2-fold change in either direction and p-value of 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may play an important role in tumorigenesis of MCPyV-negative MCC. Functional and clinical validation studies are needed to determine whether this tumor suppressor pathway represents an avenue for targeted therapy.
Publication Title
Distinct gene expression profiles of viral- and nonviral-associated merkel cell carcinoma revealed by transcriptome analysis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34
Publication Title
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique.
Publication Title
Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This study was performed to identify gene expression differences in not otherwise specified soft tissue sarcomas (NOS, malignant fibrous histiocytomas) and correlate them to histological findings and the clinical course. RNA was isolated and differential gene expression was analysed by the microarray technique.
Publication Title
Malignant fibrous histiocytoma--pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We assessed the apoptotic and antiproliferative effects of resveratrol, pycnogenol and its metabolites on HT1080 human fibrosarcoma cells in vitro. Viability, apoptosis and necrosis were quantified by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray. Cell proliferation was analysed by BrdU ELISA assay.
Publication Title
Resveratrol induces apoptosis and alters gene expression in human fibrosarcoma cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of the beta2 adrenergic receptor (2AR) after stroke is unclear as pharmacological manipulations of the 2AR have produced contradictory results. We previously showed that mice deficient in the 2AR (2KO) had smaller infarcts compared to wild-type mice (FVB) after middle cerebral artery occlusion (MCAO), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell death were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischemia (Ccl9, Gem, and Prg4). In addition to networks that were similar between genotypes, one network with a central node of G protein-coupled receptor and including biological functions carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in 2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype in all conditions. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in 2KO mice. As both genes are implicated in NFB signaling, we measured p65 activity and tumor necrosis factor alpha (TNF) levels 24h after MCAO. MCAO-induced p65 activation and post-ischemic TNF production were both greater in FVB compared to 2KO mice. These results suggest that loss of 2AR signaling results in a neuroprotective phenotype in part due to decreased NFB signaling, decreased inflammation, and decreased apoptotic signaling in the brain.
Publication Title
Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatocyte nuclear factor-4 (HNF4, NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4 in the steady state remains to be elucidated. Here we report the native HNF4 isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4 and Hepatocyte nuclear factor-4 was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4 and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation.
Publication Title
Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatocyte nuclear factor-4 (HNF4, NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4 in the steady state remains to be elucidated. Here we report the native HNF4 isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4 and Hepatocyte nuclear factor-4 was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4 and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation.
Publication Title
Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
IlluminaHiSeq2500
Description
Chromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer. Overall design: mRNA of LATS2 KO HeLa-S3 cells rescued by empty vector, wild-type LATS2 or kinase-dead LATS2 were subjected to deep sequencing profiling using Illumina HiSeq 2500
Publication Title
LATS2 Positively Regulates Polycomb Repressive Complex 2.
Sample Metadata Fields
No sample metadata fields
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