The goal of this study was to determine the effects of dietary selenium levels on translational control of selenoprotein synthesis in mouse liver. Overall design: Wild type mice and mice expressing a mutant Sec-tRNA gene (TrspA37G) were fed diets supplemented with 0, 0.1, or 2 ppm selenium for 6 weeks. Livers were harvested and ribosome and mRNA profiles were generated by deep-sequencing using the Illumina HiSeq 2000.
Translational redefinition of UGA codons is regulated by selenium availability.
Age, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
Sex, Specimen part
View SamplesMice were fed Se-deficient or Se-adequate diets for 6 weeks. Liver and lung tissue were harvested and processed for RNA-Seq, ribosome profiling, and microarray analysis. From these studies, we identified changes in mRNA levels and translation of selenoprotein genes and genes regulated by interferon-gamma. Cytokine profiles of serum indicated that interferon-gamma and IL-6 levels were increased in the Se-adequate mice relative to Se-deficient mice.
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
Sex, Specimen part
View SamplesMice were fed Se-deficient or Se-adequate diets for 6 weeks. Liver and lung tissue were harvested and processed for RNA-Seq, ribosome profiling, and microarray analysis. From these studies, we identified changes in mRNA levels and translation of selenoprotein genes and genes regulated by interferon-gamma. Cytokine profiles of serum indicated that interferon-gamma and IL-6 levels were increased in the Se-adequate mice relative to Se-deficient mice. Overall design: Ribosome profiling of liver tissue from mice fed Se-deficient or Se-adequate diets
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
No sample metadata fields
View SamplesMice were fed Se-deficient or Se-adequate diets for 6 weeks. Liver and lung tissue were harvested and processed for RNA-Seq, ribosome profiling, and microarray analysis. From these studies, we identified changes in mRNA levels and translation of selenoprotein genes and genes regulated by interferon-gamma. Cytokine profiles of serum indicated that interferon-gamma and IL-6 levels were increased in the Se-adequate mice relative to Se-deficient mice. Overall design: RNA-Seq analysis of liver tissue from mice fed Se-deficient or Se-adequate diets
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
No sample metadata fields
View SamplesSelenium has cancer preventive activity that is mediated, in part, through selenoproteins. The role of the 15 kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with shRNA constructs targeting Sep15. Metabolic 75Se-labeling and Northern and Western blot analyses revealed that more than 90% of Sep15 was knocked down. Growth of the resulting Sep15-deficient CT26 cells was reduced (p<0.01) and cells formed significantly (p<0.001) fewer colonies in soft agar compared to control CT26 cells. Whereas most (14/15) BALB/c mice injected with control cells developed tumors, few (3/30) mice injected with Sep15 knockdown cells developed tumors (p<0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases/mouse; however, mice injected with the Sep15 knockdown cells only had 7.8 +/- 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1045 genes that were significantly (p<0.001) affected by Sep15 deficiency. The highest scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G2/M cell cycle arrest in Sep15 CT26 knockdown cells. In contrast, to CT26 cells Sep15 knockdown in Lewis Lung Carcinoma (LLC1) cells did not affect anchorage-dependent or independent cell growth. These data suggest tissue specificity in the cancer protective effects of Sep15 knockdown, which are mediated, at least in part, by influencing the cell cycle.
Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells.
Specimen part, Cell line
View SamplesSelenophosphate, which is the active donor of selenium in selenocysteine (Sec) biosynthesis is synthesized from selenite and ATP by an enzyme designated as selenophosphate synthetase (SPS).There are two isoforms of SPS in higher eukaryotes,SPS1 and SPS2. Initially, both SPS1 and SPS2 were thought to be involved in selenophosphate synthesis. However, it was subsequently shown that only SPS2 catalyzes selenophosphate synthesis. Although SPS1 is an essential gene in Drosophila, its function has not been determined.
Elevation of glutamine level by selenophosphate synthetase 1 knockdown induces megamitochondrial formation in Drosophila cells.
Cell line
View SamplesAnalysis of peripheral blood mononuclear cells (PBMCs) separated from whole blood of healthy male subjects
Effects of exercise on gene expression in human peripheral blood mononuclear cells.
No sample metadata fields
View SamplesComparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.
Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression.
Sex, Treatment
View SamplesSelenoproteins mediate the cancer-preventive properties of the essential nutrient selenium, but also have cancer-promoting effects. We examined the contributions of the 15-kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and cancer metastasis of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially the interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient cells. In contrast, the Wnt/Beta-catenin pathway was up-regulated in cells that lacked both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, and controversial results of recent human clinical trials involving dietary selenium, our results are important to general public health.
The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.
Specimen part, Cell line
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