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GSE150909
Homo sapiens
9 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Genomic instability predisposes cells to malignant transformation, however the molecular mechanisms that allow for the propagation of cells with a high-degree of genomic instability remains unclear. Here we report that miR-181a is able to transform fallopian tube secretory epithelial cells- the precursor cell type for the majority of high-grade serous ovarian cancers- through the inhibition of RB1 and simultaneously drives a cell protective inhibition of the stimulator-of-interferon-genes (STING) in order to maintain a microenvironment conducive to the propagation of cells with a high-degree of genomic instability. We found that miR-181a inhibition of RB1 leads to profound nuclear defects, genomic instability, and nuclear rupture resulting in a persistence of genomic material in the cytoplasm. While normally, this persistence of genomic material in the cytoplasm induces interferon response through STING to drive cell death, miR-181a directly downregulates STING and prevents apoptosis. The most common mechanism by which oncogenic miRNAs promote tumorigenesis is through the direct inhibition of tumor suppressor genes, however our studies highlight a new mechanism of oncomiR transformation through the combination of tumor suppressor gene inhibition and abrogation of immune surveillance that initiates and propagates tumor cell survival. Importantly, we found that miR-181a induction in ovarian patient tumors is tightly associated with decreased IFNg response and downregulation of lymphocyte infiltration amd leukocyte fraction. To date, DNA oncoviruses are the only known inhibitors of STING that allow for cellular transformation thus, our findings are the first to identify a genetic factor, miR-181a, that can downregulate STING expression, suppress activation of the immunosurveillance machinery, and impair signaling in cancer cells creating a survival advantage. Our studies support the notion that the induction of STING-mediated signaling in cancer cells could lead directly to cancer cell death however these effects are abrogated by miR-181a. Given the recent interest in the development of STING agonists as a strategy to harness the immune system to treat cancer, this study introduces novel patient selective biomarker as well as potent therapeutic target for development of the most effective combination treatments.
Publication Title
miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Leptin binding to the leptin receptor (LepR) causes rapid signaling to the nucleus. We investigated the early (2 hr) transcriptional response to acute leptin injectio (intracerebroventricular)
Publication Title
Ancient origins and evolutionary conservation of intracellular and neural signaling pathways engaged by the leptin receptor.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Skin squamous cell carcinomas are among the most frequent human cancers. In this study we compared the expression profiles of 10 skin SCCs with a set of 3 normal human epidermis controls.
Publication Title
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens, Rattus norvegicus
- 34 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Significant qualitative and quantitative differences exist between humans and the animal models used in research. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Significant qualitative and quantitative differences exist between humans and the animal models used in research. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human.
Publication Title
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice are all more sensitive than wild type (WT) mice to dextran sulfate sodium (DSS)-induced colitis. The purpose of this study was to determine which genes are differentially induced by DSS treatment in the colon of Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice compared to WT mice. The results demonstrate higher induction of proinflammatory gene expression in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice than in WT mice after DSS treatment. The majority of genes whose expression is increased in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice but not in WT mice are interferon-inducible genes. Thus, Peptidoglycan Recognition Proteins Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4 protect mice from excessive inflammatory response and damage to the colon by limiting expression of interferon-inducible genes in the colon.
Publication Title
Peptidoglycan recognition proteins protect mice from experimental colitis by promoting normal gut flora and preventing induction of interferon-gamma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 49 Downloadable Samples
Illumina HiSeq 2500, NextSeq 500
Description
Purpose: the goal of this study was to test whether the amounts of genome-encoded Line-1s are influenced by TUTases and Mov10 Methods: RNA-Seq data were obtained for PA-1 or Hek293 Flp-IN T-Rex cells in which wild-type or mutant TUTases or Mov10 were overexpressed or the proteins were depleted by RNA interference Results: Minor changes (less than 0.4-fold) were observed in the amounts of mRNAs of Homo sapiens-specific Line-1 families in Hek293 Flp-IN T-Rex and PA-1 either overexpressing or depleted of TUTases and Mov10 Overall design: LINE-1 repetitive elements profiles of Hek293 Flp-IN T-Rex and PA-1 generated by deep sequencing, in triplicate, using Illumina NextSeq 500 and Illumina HiSeq 2500.
Publication Title
Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s.
Sample Metadata Fields
Cell line, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Choroid plexuses (CP) develop early during development. They form a barrier between the blood and the cerebrospinal fluid, and fulfill important protective and nutritive functions. We used Affymetrix microarrays to assess whether CP of the lateral ventricles (LVCP) have similar functions in developing and adult brain. We identified distinct families of protective and transport genes and found that most of these genes were already well expressed during development.
Publication Title
Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
To assay the effect of depletion of the RNA exosome on RNAs shorter than the standard length captured by RNA-seq (>200 nt), we created RNA-seq libraries using fragmented RNA and a linker-ligation-based protocol that does not deplete RNAs shorter than 200 nt. Note: these data relate to Figure 6E in Lubas, Andersen et al., Cell Reports 2014 (accepted) Overall design: These samples constitute RNA-seq libraries prepared to enrich for short RNA fragments such as snRNA and snoRNAs. Three different HeLa cell RNAi experiments were used to generate the RNA samples applied in the library construction: control transfected, hRRP40-depleted and triple-depleted of the known RNA exosome-associated ribonucleases (DIS3, DIS3L and hRRP6 knock-down). By these means the data offers reveal RNA exosome substrates via their up-regulation in the respective knock-downs NOTE: The ''Figure6E_RNAseq_DataTable_PlottedValues.txt'' was generated from total 5 samples, with two additional published samples [SRP031620] and provided to better allow readers to fully replicate the analyses presented in the publication.
Publication Title
The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
Sample Metadata Fields
No sample metadata fields
View Samples