eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the requirement for eIF4E dose at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we surprisingly found that 50% reduction in eIF4E, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation and tumorigenesis. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for eIF4E dose specifically in translating a network of mRNAs enriched for a unique 5UTR signature. In particular, we demonstrate that eIF4E dose is essential for translating mRNAs regulating reactive oxygen species (ROS) that fuel transformation and cancer cell survival in vivo. Therefore, mammalian cells have evolved surplus eIF4E levels that cancer cells hijack to drive a translational program supporting tumorigenesis
Differential Requirements for eIF4E Dose in Normal Development and Cancer.
Specimen part
View SamplesThe rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix.
Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons.
Cell line
View SamplesWe used microarray analysis to identify specific molecular mechanisms controlling Th17 cell differentiation in HFD mice
Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1.
Specimen part
View SamplesInhibition of miR-361-3p by locked nucleic acid (LNA)/DNA antisense oligonucleotide markedly suppressed the growth of GFP-SAS cells.
MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma.
Specimen part, Cell line
View SamplesTo identify novel Peroxisome Proliferator-Activated Receptor gamma (PPARg) responsive secretory and/or transmembrane genes that is related to obesity, we integrated the expression data from the adipose tissue derived from obese mice with the other two data sets: expression profiling of adipocyte differentiation using ST2 cells and siRNA-mediated knockdown of Pparg during ST2 cell adipogenesis.
Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.
Specimen part
View SamplesHormones and growth factors accelerate cell proliferation of breast cancer cells, and these molecules are well investigated targets for drug development and application. The mechanisms of cell proliferation of breast cancers lacking estrogen receptor (ER) and HER2 have not been fully understood. The purpose of the present study is to find genes that are differentially expressed in breast cancers and that might significantly contribute to cell proliferation in these cancers. Forty tumor samples, consisting of ten each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancer were analyzed using oligonucleotide microarrays. Both genes and tumor samples were subjected to hierarchical clustering. ER(+)/HER2(-) breast cancers and ER(-)/HER2(-) cancers tended to form a tumor cluster, but HER2 positive breast cancers were split into different tumor clusters.
Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome.
No sample metadata fields
View SamplesIn addition to transcriptional regulation, mRNA degradation critically contributes to gene expression as shown by various biological analysis. The CCR4-NOT complex serves as a major deadenylase that initiates mRNA degradation.
CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins.
Specimen part, Time
View SamplesWe have examined the changes in gene expression aftert reatment of A549 cells, a cultured alveolar epithelial cells, with flagellin and transforming growth factor beta 1.
Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells.
Specimen part, Cell line
View SamplesLymph nodes (LN) are constructed of intricate networks of endothelial and mesenchymal stromal cells. These include the fibroblastic reticular cells (FRC), lymphatic endothelial cells (LEC) and blood endothelial cells (BEC). We performed a comprehensive analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly. Infection induced rapid transcriptional regulation of large numbers of both shared and unique genes in FRC, LEC and BEC to support LN remodeling and the immune response. This transcriptional program was transient, returning to homeostasis within one month of infection. Yet, expanded FRC networks persisted for greater than three months after infection. Our results reveal the complexity of LN stromal cell responses during infection and suggest that LN remodeling to acute infection supports successive immune responses.
Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge.
Sex, Specimen part
View SamplesRecent studies have highlighted the role of adrenal corticosteroid signaling in cardiac physiology and pathophysiology. It is known that glucocorticoids and aldosterone are able to bind glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and these ligand-receptor interactions are redundant. Therefore, it has been impossible to delineate how these nuclear receptors couple with corticosteroid ligands and differentially regulate gene expression for operation of their distinct functions in the heart.
Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism.
No sample metadata fields
View Samples