To help define the genes associated with mucus synthesis and secretion in the human small airway epithelium, we hypothesized that comparison of the transcriptomes of the small airway epithelium of individuals that express high vs low levels of MUC5AC, a major secretory mucin and the major component of airway mucus, could be used as a probe to identify the genes related to human small airway mucus production / secretion. Genome-wide comparison between healthy nonsmokers grouped as high MUC5AC expressors vs low MUC5AC expressors identified significantly up-regulated and down-regulated genes in the high vs low expressors. Based on the literature, genes in the up-regulated list were used to identify a 73 MUC5AC-associated core gene list with 9 categories: mucus components; mucus-producing cell differentiation-related transcription factor; mucus-producing cell differentiation-related pathway or mediator; post-translational modification of mucin; vesicle transport; endoplasmic reticulum stress-related; secretory granule-associated; mucus secretion-related regulator and mucus hypersecretory-related ion channel. The identification of the genes associated with increased small airway mucin production in humans should be useful in identifying therapeutic targets to treat small airway mucus hypersecretion.
Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers.
Specimen part, Race, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of OSGIN1 in mediating smoking-induced autophagy in the human airway epithelium.
Specimen part, Race
View SamplesEnhanced autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the small airway epithelium to identify smoking up-regulated genes known to re-spond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 as significantly up-regulated by smoking in both the large and small airway epithelium (1.8-fold, p<0.01, 2.1-fold, p<10-4, respectively), an observation confirmed by an independent small airway microarray cohort, TaqMan PCR and RNAseq. Genome-wide correlation of RNAseq analysis of airway basal/progenitor cells isolated from healthy subjects (n=17) showed a direct correlation of OSGIN1 mRNA levels to multiple classic autophagy genes, including, LC3B, P62, WIPI1 and ATG13 (all rho>0.7, p<0.01). In vitro cigarette smoke extract exposure of nonsmoker primary airway basal/progenitor cells was accompanied by a dose-dependent up-regulation of OSGIN1 and autophagy induction. Lentivirus-mediated enhanced expression of OSGIN1 in human primary basal/progenitor cells induced puncta-like staining of LC3B and up-regulation of LC3B mRNA and protein and P62 mRNA expression level in a dose and time-dependent manner. OSGIN1-induction of autophagosome / amphistome / autolysosome formation was confirmed by co-localization of LC3B with P62 or CD63 (endosome marker) and LAMP1 (lysosome marker). Induction of autophagy by OSGIN1 is accompanied with heightened oxidative stress. Together, these observations support the concept that smoking-induced up-regulation of OSGIN1 is at least one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium.
Role of OSGIN1 in mediating smoking-induced autophagy in the human airway epithelium.
Specimen part, Race
View SamplesEnhanced autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the small airway epithelium to identify smoking up-regulated genes known to re-spond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 as significantly up-regulated by smoking in both the large and small airway epithelium (1.8-fold, p<0.01, 2.1-fold, p<10-4, respectively), an observation confirmed by an independent small airway microarray cohort, TaqMan PCR and RNAseq. Genome-wide correlation of RNAseq analysis of airway basal/progenitor cells isolated from healthy subjects (n=17) showed a direct correlation of OSGIN1 mRNA levels to multiple classic autophagy genes, including, LC3B, P62, WIPI1 and ATG13 (all rho>0.7, p<0.01). In vitro cigarette smoke extract exposure of nonsmoker primary airway basal/progenitor cells was accompanied by a dose-dependent up-regulation of OSGIN1 and autophagy induction. Lentivirus-mediated enhanced expression of OSGIN1 in human primary basal/progenitor cells induced puncta-like staining of LC3B and up-regulation of LC3B mRNA and protein and P62 mRNA expression level in a dose and time-dependent manner. OSGIN1-induction of autophagosome / amphistome / autolysosome formation was confirmed by co-localization of LC3B with P62 or CD63 (endosome marker) and LAMP1 (lysosome marker). Induction of autophagy by OSGIN1 is accompanied with heightened oxidative stress. Together, these observations support the concept that smoking-induced up-regulation of OSGIN1 is at least one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium. Overall design: Airway epithelium transcriptome analysis suggested that OSGIN, an oxidative response and cell death induction gene, was up-regulated by cigarette smoking and might be involved in autophagy regulation. In vitro study demonstrated that smoking can increase OSGIN1 expression and enhanced-expression of OSGIN1 led to autophagy, which is accompanied with heightened oxidative stress.
Role of OSGIN1 in mediating smoking-induced autophagy in the human airway epithelium.
No sample metadata fields
View SamplesExperiment: Establishment of expression profiles in a brain metastasis from a PTC (RNA processing and hybridization to Affymetrix microarray done twice to yield a technical replicate), in non-brain metastatic, stage III and IV PTCs, and primary brain tumors. Biostatistics analysis identified genes and biofunctions related to the brain metastatic PTC.
Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma.
Sex, Disease stage
View SamplesExperiment: Establishment of expression profiles in HT, PTC with HT, PTC without HT, and mPTC in comparison to TN samples. TN samples were downloaded as CEL files from the repository of the microarray vendor. Biostatistical analysis focussed in first instance on identifying genes and biofunctions related to HT and PTC with HT.
Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.
Sex, Disease
View SamplesIn order to identify potential genes that may play an important role in progression of colorectal carcinoma, we screened and validated the global gene expression using cDNA expression array on 36 CRC tissues and compared with 24 non-cancerous colorectal tissue.
Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy.
Sex
View SamplesExperiment: Expression profiling in breast cancer brain metastases (BC) compared to breast cancers (BC) and primary brain tumors (prBT). The objectives are to identify expression profiles that are specific to BCBM in order to identify new molecular biomarkers. The characterization of the BCBM samples included adjacent genetic techniques.
Comprehensive molecular biomarker identification in breast cancer brain metastases.
Sex, Specimen part, Disease stage
View SamplesCumulus cells are biologically distinct from other follicular cells and perform specialized roles, transmitting signals within the ovary and supporting oocyte maturation during follicular development. The bi-directional communication between the oocyte and the surrounding cumulus cells is crucial for the acquisition of oocyte competence. Using Illumina/deep-sequencing technology, we dissected the small RNAome of pooled human mature MII oocytes and cumulus cells. Overall design: Cumulus cells and MII mature oocytes small RNA profiles were generated by deep-sequencing, using Illumina 1G sequencer
MicroRNAs: new candidates for the regulation of the human cumulus-oocyte complex.
Specimen part, Subject
View SamplesWe recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the carbon monoxide releasing molecule, CORM-2. The E. coli microarray analysis shows that E. coli CORM-2 response is multifaceted with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in posttranslational modification, such as chaperones. CORM-2 has higher impact in E. coli cells grown anaerobically, as judged by the existence of repressed genes belonging to eight functional classes which are absent in aerobically CORM-2 treated cells. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.
Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
No sample metadata fields
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