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GSE38832
Homo sapiens
120 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Colorectal carcinoma is the third leading cause of cancer-related death in the United States. In order to understand the mechanism/signaling pathways responsible for invasion, migration and metastasis in colorectal cancer, we developed an integrative and comparative genetic approach to infer transcriptional regulatory mechanisms underlying colon cancer progression. Accordingly, we filtered fourteen human colorectal cancer (CRC) microarray data sets, from an immune competent mouse model of metastasis to identify known and novel transcriptional regulators in CRC. Using this approach, Nuclear Factor of Activated T cells (NFAT) family of transcription factors were identified as metastasis driver of colon cancer. NFAT family of transcription factors is known to induce gene transcription in various disease processes, including carcinogenesis. We used parental and metastatic derivatives of MC38 mouse colon cancer cells (MC38Par and MC38Met, respectively) to evaluate the role of NFATc1 in cancer cell invasiveness. We found that high NFATc1 expression correlates with significantly increased (p<0.0001) Trans-Endothelial Invasion (TEI) in MC38Met cells. Conversely, RNAi-based inhibition of NFATc1 expression and functional inhibition with calcineurin inhibitor FK506 in MC38Met cells, both resulted in significant decreased TEI (p=0.0193 & p=0.0003). Furthermore, a set of predicted NFATc1 target mRNAs identified in our original analysis were downregulated by knock-down of NFATc1 or functional inhibition with FK506 in MC38Met cells. The expression level (mRNA) of predicted gene targets were high in human CRC specimens which had higher than median NFATc1 mRNA expression (n=11 out of total 22). The tumor-associated NFATc1 co-regulated gene signature is significantly correlated with both disease-specific and disease-free survival in Stage II and III CRC patients. We have successfully demonstrated a bioinformatics approach to identify a tumor promoter driver gene NFATc1. Our studies suggest a role of NFATc1 towards invasion and its co-regulated gene signature for poor outcomes in colorectal cancer.
Publication Title
Nuclear factor of activated T-cell activity is associated with metastatic capacity in colon cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 50 Downloadable Samples
Illumina HiSeq 2000
Description
We perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Total RNA-sequencing time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
Publication Title
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 45 Downloadable Samples
- Illumina HiSeq 2000
Description
We perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Ribosome profiling time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
Publication Title
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
RNA-binding proteins (RBPs) are critical regulators of gene expression and elucidating the interactions of RBPs with their RNA targets is necessary to understand how combinations of RBPs control transcriptome expression. The Quaking-related (QR) sub-family of STAR domain RBPs includes developmental regulators and tumor suppressors such as C. elegans GLD-1, which functions as a master regulator of germ line development. To understand how GLD-1 interacts with the transcriptome, we identified GLD-1 associated mRNAs by a ribonomic approach. The scale of GLD-1 mRNA interactions allowed us to determine rules governing GLD-1 target selection and to derive a predictive model where GLD-1 association with mRNA is based on the number and strength of 7-mer GLD-1 binding elements (GBEs) within UTRs. GLD-1/mRNA interactions were quantified, and predictions were verified both in vitro and in live animals, including by transplantation experiments where weak and strong GBEs imposed translational repression of increasing strength on a non-target mRNA.Importantly, this study provides a unique quantitative picture of how an RBP interacts with its mRNA targets. As combinatorial regulation by multiple RBPs is thought to regulate gene expression, quantification of RBP/mRNA interactions should be a way to predict and potentially modify biological outcomes of complex posttranscriptional regulatory networks, and our analysis suggests that such an approach is possible.
Publication Title
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal was to identify targets of the RNase REGE-1 by whole RNA sequencing. Overall design: mRNA profiling of C.elegans young adults of rege-1 knockdown or mock RNAi control performed in N2 as well as glp-1 background
Publication Title
Ribonuclease-Mediated Control of Body Fat.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Ets-4 was previously identified as a suppressor of rege-1(rrr13) phenotype. The goal of this experiment was to identify down-stream regulators of ETS-4, which facilitate this suppression. Overall design: mRNA profiling of C.elegans young adults of ets-4 knockdown or mock RNAi control in the background of rege-1(rrr13)
Publication Title
Ribonuclease-Mediated Control of Body Fat.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
We present a basic characterization of the function of Y-box binding proteins in C. elegans. Besides playing an important role for fertility in the germline (all four CEY proteins), we found that the presence of CEY-1 and CEY-4 is essential for the assembly of larger polysomes in the soma. We therefore performed ribosome-profiling in combination with total RNA sequencing in wild type and cey-1,-4 double mutant animals to globally compare mRNA levels and their translation status. Overall design: Total RNA sequencing was peformed on RNA extacted from wild type and cey-1,-4 mutant animals in duplicates. Four samples in total.
Publication Title
Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G15 coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr, and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Further, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Publication Title
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 42 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Gene expression of P. aerruginosa changes after short-term exposure to ciprofloxacin at sub-inhibitory concentrations but the effect of long-term exposure which select for the most fitted subpopulations is not known.
Publication Title
The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Clariom S Assay (clariomsrat)
Description
The study evaluates potential protective effects of cerium oxide nanoparticles (nanoceria) against oxidative stress in muscle tissue, both on ground and in space
Publication Title
Modulation of gene expression in rat muscle cells following treatment with nanoceria in different gravity regimes.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples