Genome-wide mRNA expression profiling was performed in AGS, gastric cancer cell line, upon miR-25 silencing. At 48 hours upon anti-miR-25-3p (miRNA inhibitor) and non-targeting control RNA transfection, the whole transcriptome profiling was performed in triplicates. The miR-25 silencing elevates the diffuse gastric cancer features like expression of COL1A2, expression of COL1A2 co-expressed genes, Epithelial to Mesenchymal Transition (EMT) and angiogenesis associated genes.
Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features.
Specimen part, Cell line
View SamplesSV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used MEFs expressing TAg or infected by SV40. Our analysis indicates that TAg can induce interferon-stimulated genes in MEFs and that this induction depends upon the LXCXE motif and p53 binding.
Induction of interferon-stimulated genes by Simian virus 40 T antigens.
No sample metadata fields
View SamplesThe zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity.
Transcription factor Gfi1 restricts B cell-mediated autoimmunity.
Specimen part
View SamplesEzh2 epigenetically suppresses developmentally-regulated genes. Ezh2 is highly expressed during development, including in the lung. We knocked out Ezh2 in the developing lung epithelium using a Shh-cre driver which is active in foregut endoderm prior to lung morphogenesis. Many developmentally regulated genes became derepressed in the mutant lungs, leading to defects in lung development.
Ezh2 represses the basal cell lineage during lung endoderm development.
Specimen part
View SamplesSV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
Cell-type specific regulation of gene expression by simian virus 40 T antigens.
No sample metadata fields
View SamplesTo identify potential biological functions for three lncRNAs (NANCI, LL12, and LL34) we used shRNAs to knockdown expression of lncRNAs in MLE12 cells, a cell resembling type two lung epithelial cells. This data set contains the microarrays looking at gene expression.
Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development.
Treatment
View SamplesAn RNA-seq study of altered gene expression and mutations in Ara-C resistant acute myeloid leukemia murine cell lines. The analysis of the RNA-seq data led to the identification of a large deletion within the Dck coding sequence of the B117H cell line, which produced an alternatively processed form of Dck mRNA. The RNA-seq analysis also identified the presence of an insertion mutation in Dck in the B140H cell line. The RNA-seq analysis also identified a number of significant expression changes which did not appear in a previous microarray analysis (GSE18322), as well as identified other mutations which may be contributing to Ara-C resistance. Overall design: Two highly Ara-C resistant cell lines, B117H and B140H were derived from Ara-C sensitive parental cell lines, B117P and B140P. Variations in gene expression as well identification of acquired mutations between these Ara-C resistant/sensitive sets were studied using various RNA-seq analysis tools.
Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia.
Cell line, Subject
View SamplesActivated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-? expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17-mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation. Overall design: Cells were treated with glutaminase1 inhibitor or vehicle
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.
Specimen part, Subject
View SamplesGene expression data from VHL teratomas comparing genes differentially expressed based on apoptotic response to tumor microenvironment.
Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response.
Specimen part
View Samplesconsequences of astrocytes on GSCs, gene expression profiles generated from glioblastoma stem-like cells grown alone (mono-culture) and compared to those generated 48h after the initiation of co-culture with astrocytes
Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization.
Specimen part, Subject
View Samples