RNA sequencing technology has been carried out in order to evaluate mRNA expression changes after manipulation of miR-26a in both MCF-7 and MDA-MB-231 breast cancer cell lines. Overall design: To evaluate the entire set of genes modulated by miR-26a in breast cancer, we performed RNA-seq after ectopic manipulation of this miRNA. We over-expressed miR-26a in MCF-7 epithelial cancer cell lines and also reduced its activity by stably transfecting MDA-MB-231 mesenchymal-like cancer cell lines with a specific sponge vector. GO terms and pathway enriched analysis of the transcripts that significantly change upon miR-26 ectopic manipulation implicates miR-26ab in cell cycle, apoptosis, cell spreading and cell adhesion in breast cancer
Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR.
Specimen part, Cell line, Subject
View SamplesEstrogen receptor-a (ERa) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERa target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERa binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen. Overall design: Hormone depleted MCF7 Luc or Y537S cells were treated with 10nM E2 or ethanol, as vehicle control, for 8 hours, with 3 replicates (2 replicates for Y537S + E2). RNA-seq was carried out using Illumina Hiseq 2500.
Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.
Specimen part, Subject
View SamplesmiRNAs are known to be involved in PDAC tumorigenesis, but only a few biologically relevant gene targets have been identified.
MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.
Specimen part, Subject
View SamplesPBRM1 was found to be mutated in a high percentage of clear cell RCCs. We performed knockdown of PBRM1 via siRNA and compared with scrambled control in three different RCC cell lines.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
Specimen part, Cell line, Treatment
View SamplesSeed dormancy is the inability for seeds to germinate even under favorable conditions. In the Arabidopsis Landsberg <i>erecta</i> (L<i>er</i>) ecotype, 2 weeks of dry storage, called after-ripening, is sufficient to relieve seed dormancy. Such seed is referred to as after-ripened (AR) and has a high rate of germination when imbibed. While widespread transcriptome changes have been previously observed with seed dormancy loss, this experiment was designed to characterize transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive <i>sleepy1-2</i> (<i>sly1-2</i>) mutant. The <i>SLY1</i> gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. In the <i>sly1-2</i> mutant, GA-directed DELLA proteolysis cannot occur leading to DELLA protein accumulation and increased dormancy. <i>sly1-2</i> mutant seeds are fully dormant at 2 weeks of dry storage (0% germination), but germinate well with very long after-ripening (51% germination after 19 months). <i>sly1-2</i> seed germination can also be rescued by overexpression of the GA receptor, <i>GA-INSENSITIVE DWARF1b</i> (<i>GID1b-OE</i>), which resulted in 74% germination at 2 weeks of dry storage. In this experiment, we compared seeds of wild-type L<i>er</i> at 2 weeks of dry storage (non-dormant), dormant <i>sly1-2</i> (2 weeks of dry storage; <i>sly1-2</i>(D)), long after-ripened <i>sly1-2</i> (non-dormant, 19 months of dry storage; <i>sly1-2</i>(AR)), and <i>sly1-2 GID1b-OE</i> (non-dormant, 2 weeks of dry storage). Samples were collected at two imbibition timepoints: 1) a 0h timepoint after 4 days at 4°C, and 2) a 12h timepoint after 4 days at 4°C followed by 12 hours in the light at 22°C. These timepoints were selected to capture the transcriptomes at an early and late time in Phase II of imbibition. Using this experimental design we were able to determine transcriptome differences associated with seed dormancy in the <i>sly1-2</i> mutation (L<i>er</i> wt vs <i>sly1-2</i>(D)), and changes associated with <i>sly1-2</i> dormancy loss through dry after-ripening (<i>sly1-2</i>(AR) vs <i>sly1-2</i>(D)) or through <i>GID1b</i>-overexpression (<i>sly1-2 GID1b-OE</i> vs <i>sly1-2</i>(D)). Seeds for L<i>er</i> wt, <i>sly1-2</i>(D), and <i>sly1-2 GID1b-OE</i> were grown alongside each other under the same conditions and after-ripened for 2 weeks. Seeds from <i>sly1-2</i>(AR) were grown under the same conditions in advance of the other lines to allow for the long after-ripening requirement. RNA was extracted using a phenol-chloroform-based extraction from three biological replicates per treatment.
Transcriptional mechanisms associated with seed dormancy and dormancy loss in the gibberellin-insensitive sly1-2 mutant of Arabidopsis thaliana.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
No sample metadata fields
View SamplesSystematic somatic mutation screening of 4000 genes in human clear cell renal cell carcinoma. Information on corresponding somatic mutations in each sample can be found at http://www.sanger.ac.uk/genetics/CGP/Studies/.
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
No sample metadata fields
View SamplesIschemic tolerance can be induced by numerous preconditioning stimuli, including various Toll-like receptor (TLR) ligands. We have shown previously that systemic administration of the TLR4 ligand, lipopolysaccharide (LPS) or the TLR9 ligand, unmethylated CpG ODNs prior to transient brain ischemia in mice confers substantial protection against ischemic damage. To elucidate the molecular mechanisms of preconditioning, we compared brain and blood genomic profiles in response to preconditioning with these TLR ligands and to preconditioning via exposure to brief ischemia.
Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global program of gene expression during early hESC differentiation to mesendoderm using FBS, with and without RUNX1 depletion.
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
Specimen part, Cell line
View Samples