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SRP019272
Homo sapiens
362 Downloadable Samples
Illumina HiSeq 2000
Description
The genetics of messenger RNA expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to microRNA (miRNA) expression. We examined natural variation of miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for metabolic syndrome phenotypes as part of the METSIM study. We genotyped the subjects using high-density SNP microarrays and quantified the mRNA abundance using genome-wide expression arrays and miRNA abundance using next generation sequencing. We reliably quantified 356 miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed miRNAs. We mapped the miRNA abundance as an expression quantitative trait and determined cis regulation of expression for 9 of the miRNAs and of the processing of one miRNA (miR-28). The degree of genetic variation of miRNA expression was substantially less than that of mRNAs. For the majority of the miRNAs, genetic regulation of expression was independent of the host mRNA transcript expression. We also showed that for 108 miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24 miRNAs to be significantly associated with metabolic syndrome traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit ACACB, a key fatty acid oxidation enzyme that has been shown to play a role in regulating body fat and insulin resistance in adipose tissue. Overall design: miRNA expression profiling of adipose tissue isolated from 200 humans
Publication Title
Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study, the prognostic properties of miR-205 expression levels are investigated in a well-documented prostate cancer cohort. We show that miR-205 is correlated to shortened overall survival, significantly dividing the PCa patients into high and low risk groups. Furthermore, miR-205 is shown to inversely correlate to occurrence of metastases. In situ hybridization is also performed, demonstrating high miR-205 expression in the basal cells of benign prostate tissue glands. A RIP-Chip assay using an AGO2 antibody was implemented and the miR-205 targets identified were found to be enriched in MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We also found individual targets involved in cancer and androgen receptor signaling. Ectopic levels of miR-205 are shown to decrease the level of androgen receptor both at the mRNA and protein levels in prostate cancer cell lines. This is further corroborated in the prostate cancer cohort were miR-205 expression levels in the prostatic tissues are found to inversely correlate to assessment of androgen receptor (AR) immunostaining and to serum levels of PSA, a protein regulated by AR signaling. The level of miR-205 is also found to be significantly lower in castration resistant prostate cancer patients than in hormone nave patients. Our data indicates that miR-205 is regulated by androgens and act by different mechanisms in androgen depleted settings, e.g. giving opposite effects on adhesion. Taken together these findings imply that miR-205 might have therapeutic potential especially for the castration resistant and currently untreatable form of prostate cancer.
Publication Title
miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of this project was to analyze differential expression in head and neck cancer cells with various intrinsic radiosensitivity. The gene expression profiles of the cell lines were determined using the Human Genome U133 plus 2.0 Arrays (Affymetrix, Santa Clara, CA).
Publication Title
Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses. Overall design: Cochlear samples from sham operated or adrenalectomized (ADX) CBA/Sca mice were collected every 4th hour during a 24h period and subjected to RNAseq (n=3 per time point, corresponding to a total of 36 samples).
Publication Title
Circadian Regulation of Cochlear Sensitivity to Noise by Circulating Glucocorticoids.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks.
Publication Title
Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-proteolytic ubiquitin signaling mediated by K63 ubiquitin chains plays a critical role in multiple pathways converging on NFKB activation that are key to the development and activation of immune cells. However, a complete understanding of how the regulation of ubiquitin signaling affects immune cells development and functionality is still missing. G Protein Suppressor 2 (GPS2) is a multi-functional protein that recently emerged as an important regulator of inflammation and lipid metabolism through inhibition of Ubc13 activity. Here, we have deleted GPS2 in the B cell lineage results and performed RNAseq of WT and KO splenic B cells. Overall design: RNA-seq of WT and_KO of GPS2 in Bcells.
Publication Title
Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ras and TGF-β signaling enhance cancer progression by promoting the ΔNp63 transcriptional program.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate that activation of Ras and TGF- pathways strengthens the binding of p63 to its genomic sites and modulates the expression of p63 target genes.
Publication Title
Ras and TGF-β signaling enhance cancer progression by promoting the ΔNp63 transcriptional program.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this work was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]
Publication Title
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Homo sapiens
- 107 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The Uppsala Longitudinal Study of Adult Men is a population-based study aimed at identifying risk factors for cardiovascular disease. At the time of biopsy all subjects were ~ 70yr of age
Publication Title
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.
Sample Metadata Fields
Specimen part, Subject
View Samples