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SRP055411
Homo sapiens
11 Downloadable Samples
IlluminaHiSeq2000
Description
c-MYC (MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. Like other classic oncogenes, hyperactivation of MYC leads to collateral stresses onto cancer cells, suggesting that tumors harbor unique vulnerabilities arising from oncogenic activation of MYC. Herein, we discover the spliceosome as a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene, and demonstrate that BUD31 is a splicing factor required for the assembly and catalytic activity of the spliceosome. Core spliceosomal factors (SF3B1, U2AF1, and others) associate with BUD31 and are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total pre-mRNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Importantly, genetic or pharmacologic inhibition of the spliceosome in vivo impairs survival, tumorigenicity, and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers. Overall design: Examination of intron rentention in MYC-ER HMECs, in 4 conditions
Publication Title
The spliceosome is a therapeutic vulnerability in MYC-driven cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Ion Torrent Proton
Description
We have performed sucrose-gradient-based isolation of polysomal fractions from untreated and TGF-beta treated MCF-10A and MCF7 cells, subjected these fractions to RNA-seq, and also sequenced total mRNA from each cell line in the treated and untreated condition Overall design: Examination of two different cell types in a treated and untreated state
Publication Title
CELF1 is a central node in post-transcriptional regulatory programmes underlying EMT.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
Publication Title
Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
HITS-CLIP of control and transfected cells to find direct targetting of miR-200 family to mRNA
Publication Title
Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion.
Publication Title
Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours.
Publication Title
Nutlin-3a efficacy in sarcoma predicted by transcriptomic and epigenetic profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
To study how the presence of PUFAs influences central cellular processes, and in order to perform lipidome, transcriptome and molecular studies we decided to use yeast as a model organism. We therefore co-expressed 12-desaturase and 6- desaturase genes from Mucor rouxii in S. cerevisiae with the objective to obtain a yeast strain that contains PUFAs, especially linoleic acid (LA, C18:29,12) and -linolenic acid (GLA, C18:36,9,12), in its membranes.
Publication Title
Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to assess gene expression in proliferating ovarian cancer cell lines
Publication Title
Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus, Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000, Drosophila Gene 1.0 ST Array (drogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Drosophila Gene 1.0 ST Array (drogene10st)
Description
We report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes.
Publication Title
Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway.
Sample Metadata Fields
Specimen part
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