Patients with oncogene driven tumors are currently treated with targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors. The inhibited oncogenic pathway often interacts with other signaling pathways and alters predicted therapeutic response. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates pervasive molecular alterations to EGFR, MAPK, and PI3K signaling in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to infer the complex pathway interactions that result from EGFR inhibitor use in cancer cells that contain these these common EGFR network genetic alterations. To do this, we modified the HaCaT keratinocyte cell line model of premalignancy to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background. We then measured gene expression after treating modified HaCaT cells with three EGFR targeted agents (gefitinib, afatinib, and cetuximab) for 24 hours.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Cell line, Treatment
View SamplesTo determine the expression AP2-alpha target genes, global gene expression of 7 HNSCC cell lines with and without cetuximab treatment (100 nM, 24 hrs) and the HaCaT keratinocyte cell line was performed.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Specimen part, Cell line
View SamplesBackground: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance Overall design: Differential RNA-seq profiling from triplicate biological replicates of MCF7 cells treated with scrambled siRNA or siZNF217.
Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha.
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View SamplesH929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours.
The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties.
Specimen part, Treatment, Subject
View SamplesIn this study, we hypothesized that IL-27 could induce the expression of novel miRNAs in macrophages which may have functional relevance in terms of anti-viral activity. In this study, primary monocytes were differentiated into macrophages using M-CSF (M-Mac) or with a combination of M-CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted from these cells and deep sequencing was performed, in parallel with gene expression microarrays. Using the novel miRNA discovery software, miRDeep, seven novel miRNAs were discovered in the macrophages, four of which were expressed higher in I-Mac (miRNAs 2.1, 8.1, 9.1 and 14.2) whilst three were detected in both M-Mac and I-Mac (miRNAs 9.3, 13.6 and 15.8). The expression of six of the seven novel miRNAs was highly correlated with qRT-PCR using specific primer/probes designed for the novel miRNAs. Gene expression microarray further demonstrated that a number of genes were potentially targeted by these differentially expressed novel miRNAs.
Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties.
Specimen part, Treatment
View SamplesIn this study, we hypothesized that IL-27 could induce the expression of novel miRNAs in macrophages which may have functional relevance in terms of anti-viral activity. In this study, primary monocytes were differentiated into macrophages using M-CSF (M-Mac) or with a combination of M-CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted from these cells and deep sequencing was performed, in parallel with gene expression microarrays. Using the novel miRNA discovery software, miRDeep, seven novel miRNAs were discovered in the macrophages, four of which were expressed higher in I-Mac (miRNAs 2.1, 8.1, 9.1 and 14.2) whilst three were detected in both M-Mac and I-Mac (miRNAs 9.3, 13.6 and 15.8). The expression of six of the seven novel miRNAs was highly correlated with qRT-PCR using specific primer/probes designed for the novel miRNAs. Gene expression microarray further demonstrated that a number of genes were potentially targeted by these differentially expressed novel miRNAs. Overall design: screening novel and known miRNAs which may have antiviral properties in 2 different treatments in 2 donors.
Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties.
Specimen part, Subject
View SamplesThere is an association between transcriptome and the exercise-related phenotype. Peripheral blood cells suffer alterations in the gene expression pattern in response to perturbations caused by exercise. The acute response to endurance activates stress and inflammation, as well as growth and tissue repair responses.
PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesA limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. In the gustatory system, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles but exert their effects through the same receptors (TrkB and p75).
BDNF and NT4 play interchangeable roles in gustatory development.
Specimen part
View SamplesThe root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays. Single root tip zones can be used for full transcriptome analysis; further, the root apex zones are functionally very distinct from each other. RNA-Seq provided novel information about the transcripts compared to the arrays. These data will help optimize transcriptome techniques for dealing with small, rare samples. Overall design: Arabidopsis thaliana var. Columbia (COL-0) seedlings were grown on sterile solid media plates containing 0.5 % phytagel. The plates were vertically placed in growth chambers with continuous light (80-100 µmol m -2) at a constant temperature of 19° C. Eight day old seedlings were harvested into RNA-later solution in a 50 mL centrifuge tubes and stored at -20 °C freezer. The root tips were dissected into zone-I: 0.5mm from the tip including the root cap and root division zones, and zone-II: 1.5mm sections including root elongation and root hair zone. Microarray and sequencing experiments were performed.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part, Subject
View Samples