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GSE10063
Homo sapiens
58 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to being causally linked to the formation of multiple tumor types, tobacco use has been associated with decreased anticancer treatment efficacy and reduced survival time. A detailed understanding of the cellular mechanisms that are affected by tobacco smoke should facilitate the development of improved preventive and therapeutic strategies. We have investigated the effects of a tobacco smoke (TS) extract on the transcriptome of MSK-Leuk1 cells, a cellular model of oral leukoplakia. Using Affymetrix HGU133 Plus 2 arrays, 411 differentially expressed probesets were identified. The observed transcriptome changes were grouped according to functional information, and translated into molecular interaction network maps and signaling pathways. Pathways related to cellular proliferation, inflammation, apoptosis and tissue injury appeared to be perturbed. Analysis of networks connecting the affected genes identified specific molecular interactions, hubs and key transcription regulators affected by TS. Thus TS was found to induce several EGFR ligands forming an EGFR-centered molecular interaction network, as well as several AhR-dependent genes, including the xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Notably, the latter findings in vitro are consistent with our parallel finding that levels of CYP1A1 and CYP1B1 were increased in oral mucosa of smokers. Collectively, these results offer insights into the mechanisms underlying the procarcinogenic effects of TS and raise the possibility that inhibitors of EGFR or AhR signaling will prevent or delay the development of tobacco smoke-related tumors. Moreover, the inductive effects of TS on xenobiotic metabolizing enzymes may help explain reduced efficacy of chemotherapy, and suggest targets for chemopreventive agents in smokers.
Publication Title
Effects of tobacco smoke on gene expression and cellular pathways in a cellular model of oral leukoplakia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
With a model mimicking GBM tumor cell dispersal, transcriptome changes between core (immotile) and dispersive (motile) cells were analyzed. Many genes are differentially expressed between these populations. This study focused on the genes that are significantly upregulated in dispersive cells. Besides gene sets related with the cell cycle and cell survival, epithelial to mesenchymal transition gene set is upregulated in dispersive cells. In this gene set, this study identified SERPINE1 gene as an important regulator of GBM cell dispersal. Overall design: Examination of core and dispersive populations' transcriptome during U373 cell spheroid dispersal. 2 sets of samples were prepared each for core and dispersive cells.
Publication Title
Identification of <i>SERPINE1</i> as a Regulator of Glioblastoma Cell Dispersal with Transcriptome Profiling.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 1021 Downloadable Samples
- Illumina HiSeq 4000
Description
RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals in order to assess associated signatures Overall design: RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals, extracted from PAXgene RNA blood solution with the PAXgene Blood RNA Kit using DNase digestion and an additional clean-up using RNEasy MinElute kit.
Publication Title
Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection.
Sample Metadata Fields
Sex, Age, Subject, Time
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
40 current smokers and 40 age- and gender- matched never smokers underwent buccal biopsies.The study had four objectives: (a) to define the effects of smoking on the transcriptome of oral epithelial cells; (b) to determine if any of the effects of tobacco smoke on the transcriptome are gender-dependent; (c) to compare the effects of tobacco smoke exposure on the transcriptome in oral v. bronchial epithelium and (d) to identify agents with the potential to suppress the effects of tobacco smoke on the transcriptome.
Publication Title
Effects of cigarette smoke on the human oral mucosal transcriptome.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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
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