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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- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA target prediction by expression analysis of host genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Total RNA samples from three biological replicates in which the hsa-mir-26b was overexpressed in HeLa cells were profiled by gene expression. As negative control, we used total RNA samples from HeLa cells transfected with cel-mir-67
Publication Title
MicroRNA target prediction by expression analysis of host genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Total RNA samples from three biological replicates in which the hsa-mir-98 was overexpressed in HeLa cells were profiled by gene expression. As negative control, we used total RNA samples from HeLa cells transfected with cel-mir-67
Publication Title
MicroRNA target prediction by expression analysis of host genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Total RNA samples from Vax2 knockout mouse eyes (at least two biological replicates) were profiled by gene expression. As control we used total RNA from wild type eyes. The analysis was carried out at five different developmental stages: E10.5, E12.5, E16.5, P8, and P60.
Publication Title
Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.
Publication Title
Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 114 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
An increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.
Publication Title
Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.
Sample Metadata Fields
Sex, Specimen part
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GSE46317- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gliogenesis in the Drosophila CNS occurs during embryogenesis and also during the postembryonic larval stages. Several glial subtypes are generated in the postembryonic CNS through the proliferation of differentiated glial cells. The genes and molecular pathways that regulate glial proliferation in the postembryonic CNS are poorly understood. In this study we aimed to use gene expressing profiling of CNS tissue enriched in glia to identify genes expressed in glial cells in the postembryonic CNS.
Publication Title
Glial enriched gene expression profiling identifies novel factors regulating the proliferation of specific glial subtypes in the Drosophila brain.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of nave and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than nave B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not nave B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool.
Publication Title
Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cells were isolated from healthy human donors (n=2). Unstimulated cells. Cells were stained with CD4, CD45RA, CCR7 and CXCR7. Using flow cytometry, 4 CD4+ T cell populations were sorted: (1) Nave (CD45RA+CCR7+CXCR5-), (2) Central memory (CD45RA-CCR7+CXCR5-), (3) Effector memory (CD45RA-CCR7-CXCR5-) and (4) CXCR5+ cells (CD45RA-CCR7-CXCR5+)
Publication Title
CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.
Sample Metadata Fields
Specimen part
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