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Transcriptome profiles associated with selenium deficiency dependent oxidative stress identify potential diagnostic and therapeutic targets in liver cancer cells

ABSTRACT: Hepatocellular carcinoma (HCC) cells show increased resistance to various stress conditions such as oxidative stress. Conventional therapies have low efficacies due to resistance and off-target effects in HCC. Here we aimed to analyze oxidative stress-related gene expression profiles of two HCC cell lines. To identify important genes that cause resistance to reactive oxygen species (ROS), a model of oxidative stress upon selenium (Se) deficiency was utilized in which an affymetrix microarray data was generated for two isogenic HCC cell lines - HepG2 and HepG2-2.2.15 (Head-to-Tail HBV genome integration) that are either sensitive or resistant to Se deficiency dependent oxidative stress, respectively.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163950 | GEO | 2020/12/29

REPOSITORIES: GEO

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RNA-seq of selenium treatment in cortical neurons

Project description:Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stress by induction of a transcriptional adaptive response. Pharmacological selenium (Se) augments mitochondrial and nuclear GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1, to protect neurons. This RNA seq data uses primary cortical neurons in cultures treated with either homocysteic acid (HCA), which induces ferroptosis and/or Se, which augments the adaptation to ferroptosis. Both protective (1mM Se) and non-protective (0.1mM Se) of selenium are used. Cells are collected after 6 hours when the transcriptional response is observed.

2019-02-20 | GSE126787 | GEO

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

Project description:Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency. Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 µg Se/g diet.

2011-01-19 | GSE23895 | GEO

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

2011-01-19 | E-GEOD-23895 | biostudies-arrayexpress

Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon

Project description:Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086mg Se/kg) or a selenium-adequate (0.15mg Se/kg) diet. After 6wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.

2018-07-13 | GSE117025 | GEO

Hepatic transcriptome profiles differ among maturing beef heifers supplemented with different forms of dietary selenium

2013-06-01 | GSE44680 | GEO

Hepatic transcriptome profiles differ among maturing beef heifers supplemented with different forms of dietary selenium

Project description:Little is known regarding the relationship between Selenium (Se) concentrations in the liver and liver gene expression. Because most cow-calf operations in Se-poor soils provide enough Se in mineral mixes to avoid deficiency, the aim of this study was to determine the effects of 4 Se form supplementation strategies (none or inorganic, organic, or 1:1 inorganic:organic mix) on liver gene expression profiles using a Se-adequate model. Microarray analysis was conducted using the custom WT Btau 4.0 Array (version 1; GeneChip, Affymetrix, Inc., Santa Clara, CA, USA) to determine if dietary Se supplementation form differentially affects the hepatic gene expression profiles of maturing beef heifers. Sodium selenite was used as the source of inorganic Se and Se-enriched yeast was the source of organic selenium. Thirty-six Angus heifers (BW 400 Â± 9.0 kg) were ranked on the Se concentration of their biopsied (day -14) liver sample and randomly assigned to one of four dietary Se treatments: Control (Ctrl) group received no exogenous dietary Se supplementation; inorganic (ISe) treatment group received daily dietary Se supplementation at 3 mg/ animal of the ISe form; organic (OSe) treatment group received daily dietary Se supplementation of 3 mg/ animal of OSe form; and the mix (1:1 ISe:OSe) received daily dietary Se supplementation of 3 mg/ animal of 50:50 mix of ISe and OSe forms. RNA was extracted from biopsied liver samples taken 168 days after initiation of Se supplementation and microarray analyses were conducted.

2013-06-01 | E-GEOD-44680 | biostudies-arrayexpress

Comparative proteomic analysis of pepper (Capsicum annuum L.) seedlings under selenium stress

Project description:Selenium (Se) is an essential trace element for human and animal health. Se fertilizer has been used to increase the Se content in crops to meet the Se requirements in humans and animals. To address the challenge of Se poisoning in plants, the mechanisms underlying Se-induced stress in plants must be understood. Here, to elucidate the effects of Se stress on the protein levels in pepper, we used an integrated approach involving tandem mass tag labeling, HPLC fractionation, and mass spectrometry-based analysis. A total of 4,693 proteins were identified, 3,938 of which yielded quantitative information. Among them, the expression of 172 proteins was up-regulated, and the expression of 28 proteins was down-regulated in the Se/mock treatment comparison. According to the above data, we performed a systematic bioinformatics analysis of all identified proteins and differentially expressed proteins (DEPs). The DEPs were most strongly associated with the terms ‘metabolic process’, ‘posttranslational modification, protein turnover, chaperones,’ and ‘protein processing in endoplasmic reticulum’ according to GO, KOG classification, and KEGG enrichment analysis, respectively. Furthermore, several heat shock proteins were identified as DEPs. These results provide insights that may facilitate further studies on the pepper proteome expressed downstream of the Se stress response. Our data revealed that the responses of pepper to Se stress involve various pathways.

2019-09-16 | PXD013257 | Pride

C. Elegans expression: toxic vs. adequate vs. low selenium

Project description:Genome-wide expression analysis in C. Elegans grown in axenic media with low to toxic selenium concentrations We performed Affymetrix micorarray-based transcriptional profiling on wild-type C. Elegans Bristol N2 grown in low Se axenic media supplemented with five concentrations of selenium, from low to toxic, and harvested at the L4-larva stage. RNA was prepared for hybridization to Affy microarrays from synchronized cultures of wild-type C. elegans seeded in low Se axenic media, supplemented with graded 0, 0.05, 0.1, 0.2, and 0.4 mM Se added as sodium selenite, and harvested at the L4-larva stage (1 culture/sample per Se concentgration).

2014-07-03 | E-GEOD-54011 | biostudies-arrayexpress

Dietary selenium-methionine affects the levels and toxicity of methylmercury in Balb-C mice

Project description:Methylmercury (MeHg) is a well-known neurotoxicant, particularly harmful for the developing brain. Selenium is a nutrient previously shown to interact with MeHg, however the molecular mechanisms behind these interaction is not fully described. To explore the effect of selenium on MeHg, mice were exposed to selenomethionine (SeMet) and MeHg in a 2 x 3 full factorial design for 12 weeks. After termination, organs, including the brain, were collected for Hg and Se analysis. The hippocampus was collected and analysed using gel free proteomics and RNA sequencing (RNA-seq). The presence of SeMet reduced the amount of Hg in several organs, including the brain, while the level of Hg were increased in the feces. The presence of Hg also increased the concentration of selenium in liver and cortex. Proteomic and RNA-seq analyses showed that several known pathways of MeHg toxicity, such as oxidative stress, altered metabolism and calcium disruption were alleviated when SeMet were present. Our results suggest that SeMet can to a certain extent ameliorate the neurotoxic effects of MeHg in a mouse model. Although, whether this is due to decrease of body burden of Hg or through direct interactions with selenium in vivo remains unclear.

2020-08-29 | GSE135381 | GEO

The effects of a dietary organic selenium exposure of juvenile rainbow trout livers.

Project description:In this study, juvenile rainbow trout were exposed four dietary doses of organic selenium (7.1, 10.7 19.5 and 31.8 mg/kg Selenium) over 60 days. The RNA was exctracted from liver tissue and used for further gene expression analysis. There were 39 samples analyzed (8) control liver tissues (8) 7.1 mg/kg Se dosed fish liver tissues (7) 10.7 mg/kg Se dosed fish liver tissues (8) 19.5 mg/kg Se dosed fish liver tissues (9) 31.8 mg/kg Se dosed fish liver tissues. There was a total of 39 microarrays processed.

2015-06-30 | E-GEOD-67599 | biostudies-arrayexpress

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