Cholesterol homeostasis modulates platinum sensitivity in human ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE144248 | GEO | 2020/05/21
REPOSITORIES: GEO
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2023-12-07 | GSE141616 | GEO
Project description:The study evaluated effects of dietary cholesterol (1.5%) in Atlantic salmon fed a plant based diet for 77 days. Cholesterol supplementation did not affect growth or organ weights of Atlantic salmon, but promoted induction of cholesterol and plant sterol efflux in the intestine, whereas sterol uptake was suppressed. Microarray analyses in the liver indicated decreased cholesterol biosynthesis and enhanced conversion to bile acids. The marked effect of cholesterol on bile acid synthesis suggests that dietary cholesterol can be used to stimulate bile acid synthesis in fish. The study clearly demonstrated how Atlantic salmon adjusted metabolic functions in response to the dietary load of cholesterol, and has expanded our understanding of sterol metabolism and turnover that adds to the knowledge of these processes in fish. Atlantic salmon received feeds based on plant ingredients with (CH) and without (K) supplementation of cholesterol. Liver samples were collected after 77 days. Five individuals from each group were analyzed with microarrays, pooled liver sample of salmon fed with commerical fish meal based feed was used as a reference.
2013-10-31 | E-GEOD-51887 | biostudies-arrayexpress
Project description:The study evaluated effects of dietary cholesterol (CH), taurocholate (TC), choline (CN) and taurine (TA) in Atlantic salmon fed a plant based diet for 77 days. The additives did not affect growth or organ weights of Atlantic salmon, but promoted induction of cholesterol and plant sterol efflux in the intestine, whereas sterol uptake was suppressed. Microarray analyses in the liver indicated decreased cholesterol biosynthesis and enhanced conversion to bile acids. The marked effect of cholesterol on bile acid synthesis suggests that dietary cholesterol can be used to stimulate bile acid synthesis in fish. The study clearly demonstrated how Atlantic salmon adjusted metabolic functions in response to the dietary load of cholesterol, and has expanded our understanding of sterol metabolism and turnover that adds to the knowledge of these processes in fish. Feed supplementation with choline improved lipid absorption and suppressed abnormal accumulation of fat in the gut.
2013-10-31 | GSE51887 | GEO
Project description:Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.
2019-04-29 | GSE118451 | GEO
Project description:The molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other. We show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline or an increase in OXPHOS. Our work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.
2020-01-16 | PXD015873 | Pride
Project description:Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be defined. We therefore quantified cholesterol and phospholipid concentrations in intestine and liver and determined fecal neutral sterol and bile acid excretion in C57Bl/6N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat diet containing 0.03 % (w/w) cholesterol. To identify underlying mechanisms of dietary adaptation in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Animals on high fat diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load. The proximal part of the intestine of mice fed either a control or a high fat diet were analyzed. 5 replicates each.
2011-08-31 | E-GEOD-29748 | biostudies-arrayexpress
Project description:Ocular Sebaceous Carcinoma (OSC) is a rare malignant tumor for which initial clinical and pathological diagnosis is often incorrect. OSC can mimic Squamous Cell Carcinoma of the Conjunctiva (SCCC). Aim of this study was to find microRNA biomarkers to distinguish OSC and SCCC from normal tissue and from each other. Clinical OSC and SCCC case files and corresponding histopathological slides were collected and reviewed. Microdissected formalin-fixed paraffin-embedded tumor and control tissue were sub-jected to semi-high throughput microRNA profiling. MicroRNA expression distinguishes OSC and SCCC from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. No prognostic miRNAs could be identified that reliable predict SCCC metastasis or OSC recurrence. A com-parison between OSC (n=14) and SCCC (n=18) revealed 38 differentially expressed microRNAs (p<0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSC, n=11; SCCC, n=12). At least two miRNAs miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001) displayed a statistically significant differential expression between OSC and SCCC with miR-196b-5p upregulated in SCCC and miR-107 up-regulated in OSC. In the validation cohort microRNA miR-493-3p also showed significant up-regulation in SCCC when compared to OSC (p ≤ 0.05). ROC analyses indicated that the com-bined miR-196b-5p and miR-107 expression levels predicted OSC with 90.0% sensitivity and 83.3% specificity. In conclusion, combined testing of miR-196b-5p and miR-107, can be of additional use in routine diagnostics to discriminate OSC from SCCC.
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Project description:Farnesyl diphosphate synthase (FDPS), an essencial enzyme involved in mevalonate pathway, is implicated in cancers and osteoporosis by catalyzing head to tail condensation of two molecules of isopentenyl pyrophosphate with dimethylallyl pyrophosphate to form farnesyl pyrophosphate. It has also been identified as an RNA-binding protein (RBP). However, it’s exactly RNA-binding function in diseases, up to now, remain unknown. In the present study, the function of FDPS in HeLa cells was investigated with FDPS overexpression. The results showed that FDPS overexpression promoted proliferation in HeLa cells. FDPS overexpression extensively regulated the expression of genes in cell proliferation, cytokine-mediated signaling pathway, and extracellular matrix organization. In addition, FDPS extensively regulated the alternative splicing of numbers of genes related with osteoporosis, including NAB1, FGFR3, and ALPL, and FDPS-regulated DEGs and ASEs were highly validated by RT-qPCR. This is the first study to investigate the properties of FDPS as an RBP from a genome-wide perspective, our results suggested that FDPS acts as an RBP playing an important role in cancer progression and osteoporosis by altering gene expression and regulating alternative splicing, which contributes to a precise understanding of potentially FDPS-targeted therapies.
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