Filters
Technology
Platform
SRP078500
Homo sapiens
5 Downloadable Samples
NextSeq 500
Description
ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumors. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylated the Lysine 120 residue of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates p53' apoptotic function by upregulating HDAC6. These results indicate that pharmacological inhibition of HDAC6 is a novel therapeutic strategy involving ARID1A-mutation Overall design: RNA-seq transcription profiling of samples with altered HDAC6 activity
Publication Title
ARID1A-mutated ovarian cancers depend on HDAC6 activity.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
Publication Title
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Diabetogenic CD8+ G9C8 clone cells and the T cells from a transgenic mouse bearing the same TCR as the clone, displayed differences in their ability to induce disease in vivo.Microarray analysis was done to identify the molecular basis for such differences between the two sets of CD8 T cells.
Publication Title
Cytotoxic mechanisms employed by mouse T cells to destroy pancreatic β-cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Glycine max
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
We present results from deep sequencing of small RNA populations from several genotypes of soybean and demonstrate that the CHS siRNAs accumulated only in the seed coats of the yellow varieties having either the dominant I or i-i alleles and not in the pigmented seed coats with homozygous recessive i genotypes. However, the diagnostic CHS siRNAs did not accumulate in the cotyledons of genotypes with the dominant I or i-i alleles thus demonstrating the novelty of an endogenous inverted repeat region of CHS genes driving RNA silencing in trans of non-linked CHS family members in a tissue-specific manner. The phenomenon results in inhibition of a metabolic pathway by siRNAs in one tissue allowing expression of the flavonoid pathway and synthesis of secondary metabolites in other organs as the chalcone synthase small RNAs are found in the seed coats of yellow seeded soybean varieties but not in the cotyledons of the same genotype. Overall design: In order to compare the population of chalcone synthase related small RNAs, we sequenced 3 to 6 million small RNAs using the Illumina Genome Analyzer from the following four soybean cultivars and tissues with specific genotypes at the I locus: Richland immature seed coats (homozygous for the dominant I allele that specifies yellow seed coat); Williams immature seed coats (homozygous for the dominant i-i allele that specifies yellow seed coat with pigmented hilum) Williams (i-i/i-i yellow) immature cotyledons (homozygous for the dominant i-i allele that specifies yellow seed coat with pigmented hilum); Williams 55 immature seed coats (a Williams isogenic line homozygous for the recessive i allele that specifics pigmented seed coats. All seed coats and cotyledons were dissected from green stage immature seeds within the fresh weight range of 50-75 mg.
Publication Title
Endogenous, tissue-specific short interfering RNAs silence the chalcone synthase gene family in glycine max seed coats.
Sample Metadata Fields
Subject
View Samples- Arabidopsis thaliana
- 11 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
BACKGROUND:Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking.
Publication Title
"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 12 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000, Illumina Genome Analyzer
Description
Small RNAs (sRNAs) are hypothesized to contribute to hybrid vigor because they maintain genome integrity, contribute to genetic diversity, and control gene expression. We used Illumina sequencing to assess how sRNA populations vary between two maize inbred lines (B73, Mo17) and their hybrid. We sampled sRNAs from the seedling shoot apex and the developing ear, two rapidly growing tissues that program the greater growth of maize hybrids. We found that parental differences in siRNAs primarily originate from repeat regions. Although the maize genome contains greater number and complexity of repeats compared to Arabidopsis or rice, we confirmed that like these simpler plant genomes, 24-nt siRNAs whose abundance differs between maize parents also show a trend of downregulation following hybridization. Surprisingly, hybrid vigor is fully maintained when 24-nt siRNAs are globally reduced by mutation of the RNA-dependent RNA polymerase2 (RDR2) encoded by modifier of paramutation1 (mop1). We also discovered that 21-22nt siRNAs derived from a number of distinct retrotransposon families differentially accumulate between B73 and Mo17 as well as their hybrid. Thus, maize possesses a novel source of genetic variation for regulating both transposons and genes at a genomic scale, which may contribute to its high degree of observed heterosis. Overall design: sRNA libraries were derived from RNA isolated from the seedling shoot apex and developing ear tissues from B73, Mo17, B73xMo17 and Mo17xB73. The shoot apex was chosen because it is enriched for meristematic tissue where cell proliferation occurs, rates of organ initiation are determined, and organ size is specified. The developing ear was examined because it is enriched in meristematic tissue and is undergoing rapid growth, and also because the mature ear shows the highest degree of heterosis. Total RNA was isolated and separated on a 15% TBE-Urea polyacrylamide gel. Using a 10-bp ladder, the sRNA fraction representing 10-40-bp was excised. sRNA libraries were prepared according to Lu et al. (2007) or manufacturer''s instructitions (Illumina). A combination of Perl scripts and FASTX toolkit scripts were used to remove adapters, collapse identical sequences and count reads per sequence. Supplementary processed data text files contain the distinct sRNA sequences for all of the genotypes analyzed in that experiment. Abundance (reads per million) was calculated for each distinct sequence by dividing the number of reads of distinct sRNA in a library by the total number of sRNA reads for that library and multiplying this by 1 million. Genome builds: B73 genome, maizesequence.org release 4a.53 (October, 2009); Mo17 whole genome shotgun clones.
Publication Title
Repeat associated small RNAs vary among parents and following hybridization in maize.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 21 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
RAW264.7 mouse macrophages were transfected with negative control and miR-342-3p mimics and subjected to microarray analysis 18 hours after the transfection.
Publication Title
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to identify markers predicting responder status in tocilizumab treatment in rheumatoid arthritis in 13 patients at week 0 and week 4 of treatment.
Publication Title
Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Androgens are required for the development of normal prostate, and they are also linked to the development of prostate cancer.
Publication Title
Proteomic interrogation of androgen action in prostate cancer cells reveals roles of aminoacyl tRNA synthetases.
Sample Metadata Fields
Specimen part, Cell line
View Samples