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SRP200955
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2500
Description
Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells. Overall design: RNA-seq was used to study the effects of the D538G mutation on gene expression
Publication Title
Estrogen-independent molecular actions of mutant estrogen receptor 1 in endometrial cancer.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the transcriptome changes that result of the genomic deletion of one or two alleles of an islet-specific long non-coding RNA (Blinc1) in isolated pancreas from e15.5 mouse embryos. Overall design: Pancreas from e15.5 embryos were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq.
Publication Title
βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Multiple myeloma (MM) is a currently incurable malignancy of antibody-secreting plasma cells. Long non-coding RNAs (lncRNAs) have been recognised as an important class of regulatory molecules which are increasingly implicated in tumorigenesis. While recent studies have demonstrated changes in expression of lncRNAs in MM, the functional significance and molecular pathways downstream of these changes remain poorly characterised. In this study we have performed CRISPR-mediated deletion of the locus encoding the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE), a known oncogenic lncRNA that is overexpressed in plasma cells of MM patients and is a marker of poor prognosis. We found that CRISPR-mediated deletion of the CRNDE locus in MM cells decreases proliferation and adhesion properties, increases sensitivity to Dexamethasone and reduces tumour growth in an in vivo xenograft model. Transcriptomic profiling in CRNDE-deleted MM cells demonstrated that CRNDE activates expression of a number of genes previously implicated in the aetiology of MM, including IL6R. We further demonstrate that deletion of the CRNDE locus diminishes IL6 signalling and proliferative responses in MM cells. Altogether this study reveals the IL6 signalling pathway as a novel mechanism by which CRNDE impacts upon MM cell growth and disease progression.
Publication Title
The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina HiSeq 2000
Description
To investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Publication Title
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Publication Title
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples