Filters
Technology
Platform
GSE48463
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages.
Publication Title
Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke.
Publication Title
Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1(+) smokers with early emphysema.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
We derived a transcriptional signature of oncogenic KRAS by using the KF508 murine pancreatic ductal cell line with an inducible Lox-Stop-Lox (LSL) cassette in front of the KRASG12D oncogene to regulate transcription. This dataset allowed us to study the differential expression profile after oncogenic KRAS induction in mouse.
Publication Title
Master Regulators of Oncogenic KRAS Response in Pancreatic Cancer: An Integrative Network Biology Analysis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Zea mays
- 8 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Stalk borers are major pests for some of the most important crops in the world, such as maize or rice. Plant defense mechanisms against these herbivores have been poorly investigated. The maizes stalk responds to insect feeding activating defense genes including hormone biosynthetic-related or proteinase inhibitor transcripts. The most outstanding conclusion is that cells in the maizes stalk undergo cell wall fortification after corn borer tunneling.
Publication Title
Inducible maize defense mechanisms against the corn borer Sesamia nonagrioides: a transcriptome and biochemical approach.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Dissection of melanoma heterogeneity through gene expression profiling has led to the identification of two major phenotypes, conventionally defined as MITF high / proliferative and AXL high / invasive. Tumors or single melanoma cells characterized by a predominant AXL-related gene program show enhanced expression of sets of genes involved in motility, invasion and regulation of epithelial-mesenchymal transition (EMT), while these genes are downregulated in tumors or cells with a predominant MITF-related gene program. The activation of the AXLhi/MITFlo invasive gene program in melanoma is characterized by aberrant expression of transcription factors (TFs) involved in the embryonic EMT process. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Here we provide evidence for a new actionable pathway that controls melanoma EMT-like/invasive phenotype. We show that in MITFlo melanomas, the TF NFATc2 controls the EMT-like transcriptional program, the invasive ability of neoplastic cells, as well as in-vitro and in-vivo growth, through a pathway that functionally links c-myc to FOXM1 and EZH2. Targeting of NFATc2, FOXM1 or EZH2 inhibited melanoma migratory and invasive activity. Moreover, pharmacological co-targeting of NFATc2 and EZH2 promoted apoptosis of BRAF-mutant melanomas with intrinsic resistance to BRAF inhibition.
Publication Title
An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
HT induces an OXPHOS metabolic editing of ER+ breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133hi/ERlo cells mediating metastatic progression, which is sensitive to dual targeted therapy
Publication Title
Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
The goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Reprogramming of cancer cell metabolism toward aerobic glycolysis, i.e. the Warburg effect, is a hallmark of cancer; according to current views, the rationale for selecting such energy-inefficient metabolism is the need to increase cellular biomass to sustain production of daughter cells and proliferation. In this view, metabolic reprogramming is considered as a simple phenotypic endpoint that occurs as a consequence of signal transduction mechanisms, including oncogene-driven nutrient uptake and metabolic rewiring. A newly emerging paradigm is instead that transcriptional networks and oncogenic signaling can also be regulated downstream of metabolic pathways, that assume causative roles in controlling cancer cell behavior, above and beyond their core biochemical function. To explore possible links between glucose metabolism and nuclear gene transcription we compared immortalized mammary epithelial cells (MCF10A) and metastatic breast cancer cells (MDA-MB-231) growing in high glucose or in the presence of a widely used inhibitor of glucose uptake / glucose metabolism, 2-deoxy-glucose (2DG).
Publication Title
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Sample Metadata Fields
Cell line, Treatment
View Samples