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SRP074343
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2500
Description
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer protein that can specifically kill tumor cells while sparing healthy ones. Emerging evidences suggest that TRAIL resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at the epigenetic level is not understood. In this study, we aimed to identify novel epigenetic mechanisms regulating TRAIL response in Glioblastoma Multiforme (GBM) by a short-hairpin RNA (shRNA) screen. We employed an shRNA-mediated loss of function approach to interrogate the role of 48 genes in DNA and histone modification pathways. From this we identified KDM2B, an H3K36-specific demethylase, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity, the activation of Caspase-8, Caspase-3, Caspase-7, and cleavage of PARP. KDM2B knockdown also accelerated the apoptosis process, as revealed by live cell imaging experiments. Moreover, simultaneous knockdown of the methyltransferases responsible for generating the histone marks removed by KDM2B significantly recovered the cell death phenotype observed with KDM2B inhibition. To decipher the downstream molecular pathways regulated by KDM2B, levels of apoptosis-related genes were examined by RNA-sequencing and quantitative PCR upon KDM2B loss, which revealed de-repression of pro-apoptotic genes HRK, caspase-7, and DR4 and repression of anti-apoptotic gene Mcl-1. The apoptosis phenotype was dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. In vivo, KDM2B-silenced tumors exhibited slower growth and reduced angiogenic capacity compared to controls. Taken together, our findings suggest a novel mechanism regulating apoptotic response, where the key apoptosis components are under epigenetic control of KDM2B in GBM cells. Overall design: mRNA profiles of U87MG GBM cells transduced either by control shRNA or shRNA targeting KDM2B were generated by RNA-seq (Illumina HiSeq 2500). 2 biological replicates of shControl and shKDM2B total RNAs were barcoded individually and deep sequenced as 3 technical replicates each in 3 lanes.
Publication Title
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis, the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix).
Publication Title
Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC).
Publication Title
Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFS>50months) versus bad outcome (OS<19months and DFS<7months). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with -catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis.
Publication Title
Molecular markers associated with outcome and metastasis in human pancreatic cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 131 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
To evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.
Publication Title
Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival.
Publication Title
Human pancreatic cancer contains a side population expressing cancer stem cell-associated and prognostic genes.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: The transcription factor EVI1 regulates cellular proliferation, differentiation, and apoptosis, and contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. Methods: U937T_EVI1, a previously established human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to genome wide gene expression microarray analysis. qRT-PCR was used to confirm the regulation of MS4A3 by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and direct binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Experimental results were tested for statistical significance using ANOVA and Student's t-test (two-tailed). Results: Gene expression microarray analysis identified 27 unique genes that were up-regulated and 29 that were down-regulated in response to EVI1 induction in the human myeloid cell line, U937. The most strongly repressed gene was membrane-spanning-4-domains subfamily-A member-3 (MS4A3), and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model. Conclusions: Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
Publication Title
EVI1 promotes tumor growth via transcriptional repression of MS4A3.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk. Accordingly, we took advantage of the protective mechanisms of probiotics against lethal infection of enterohemorrhagic Escherichia coli O157:H7 in murine gnotobiote model system
Publication Title
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk To analyze the differences of gene expression between BA- or BL-associated murine colonic epithelium, we performed comparative transcriptomic analysis.
Publication Title
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
Sample Metadata Fields
No sample metadata fields
View Samples