Evaluation of the role of RIP4 in lung adenocarcinoma revealed that RIP4 inhibits STAT3 signaling in vitro and in vivo. Repression of RIP4 enhanced STAT3 signaling activation in KRAS LSL/G12D/wt; p53flox/flox murine tumors. This promoted cancer dedifferentiation through ECM remodeling
RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.
Age, Specimen part
View SamplesWT mice and Nfkb/p65 S534A were exposed to 1mg/kg LPS and their gene expression measured.
Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.
Sex, Specimen part
View SamplesWT mice and Nfkb/p65 S534A were exposed to 1g/kg LPS and their gene expression measured.
Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.
Sex, Specimen part
View SamplesDietary fatty acids have myriads of effects on human health and disease. Many of these effects are likely achieved by altering expression of genes. Several transcription factors have been shown to be responsive to fatty acids, including SREBP-1c, NF-kB, RXRs, LXRs, FXR, HNF4, and PPARs. However, the relative importance of these transcription factors in regulation of gene expression by dietary fatty acids remains unclear. Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the acute effects of individual dietary fatty acids on hepatic gene expression in mice. The dietary interventions were performed in parallel in wild-type and PPAR-/- mice, enabling the determination of the specific contribution of PPAR. Depending on chain length and degree of saturation, dietary fatty acids caused a statistically significant change in expression of over 400 genes. Surprisingly, the far majority of genes regulated by dietary fatty acids in wild-type mice were unaltered in mice lacking PPAR, indicating PPAR-dependent regulation. We conclude that the effects of dietary fatty acids on hepatic gene expression are almost entirely mediated by PPAR, indicating that PPAR dominates fatty acid-dependent gene regulation in liver.
Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Sex, Specimen part
View SamplesNeuroblastomas are tumors of the developing peripheral sympathetic nervous system, which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/beta-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/beta-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression.
Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation.
No sample metadata fields
View SamplesThe innate immune system is the organisms first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level.
Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses.
Specimen part, Cell line
View SamplesThe post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3'' untranslated regions (3''UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-Seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-Seq reads substantially increased and improved existing 3''UTR annotations, resulting in confidently identified 3''UTRs for more than 78.79% of the annotated protein-coding genes in zebrafish. Most zebrafish genes undergo alternative CPA with more than a thousand genes using different dominant 3''UTRs at different stages. 3''UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3''UTRs are highly expressed in the ovary yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3''UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At two hours post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3''UTRs provide a resource for studying gene regulation during vertebrate development. Overall design: 3P-Seq was used to map the 3'' ends of protein-coding genes in the zebrafish genome
Extensive alternative polyadenylation during zebrafish development.
No sample metadata fields
View SamplesRNA-seqs followed by miRNA transfections (miR-124 and miR-155) into four different cell lines( HeLa, HEK293, Huh7, and IMR90). Overall design: There are two biological replicates of RNA-seqs per each miRNA transfection per each sample and there are corresponding mock transfections.
Global analyses of the effect of different cellular contexts on microRNA targeting.
No sample metadata fields
View SamplesWe used microarrays to investigate the global changes of gene expression in B cells of mir-155 Knockout mice.
Global analyses of the effect of different cellular contexts on microRNA targeting.
Specimen part
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