Expression data of thermally eluted RNA from human primary fibroblasts with non-targeting or GLD4 siRNA treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE77747 | GEO | 2016/09/01
SECONDARY ACCESSION(S): PRJNA311343
REPOSITORIES: GEO
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Project description:In a screen for downregulated genes in poly(U) chromatography upon GLD4 knockdown, we identified carbohydrate metabolism genes were affected including a glucose transporter, GLUT1 human primary fibroblasts are treated with non-targeting siRNA or siGLD4. RNAs were subjected to poly(U) chromatography and eluted at 65C. Differentially expressed genes were identified using illumina microarray.
2016-09-01 | E-GEOD-77747 | biostudies-arrayexpress
Project description:Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.
2022-02-26 | E-MTAB-11160 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells. Here we performed an in vivo CRISPR screen and identified the facilitated glucose transporter type 1 (GLUT1) as a critical metabolic dependency for murine MLL::AF9 LSCs. GLUT1 disruption by genetic ablation or by pharmacological inhibition with BAY-876 led to suppression of leukemia progression and improved survival in an MLL::AF9 mouse model of AML. Glut1 inhibition further resulted in glycolytic suppression, decreased levels of tricarboxylic cycle intermediates, and elevated levels of amino acids. These changes in metabolic profile coincided with increased autophagic activity and differentiation of AML cells. Notably, dual inhibition of GLUT1 and oxidative phosphorylation exhibited synergistic anti-leukemic effects in human AML cells. Collectively, these findings increase our understanding of how murine LSCs are metabolically regulated and highlight GLUT1 inhibition as a promising therapeutic adjuvant approach in AML.
2022-07-28 | GSE209636 | GEO
Project description:Hypothesis: Overexpression of the GLUT1 facilitative glucose transporter, in A7r5 vascular smooth muscle cells, is sufficient and/or necessary to induce alterations in gene expression which influence apoptosis, growth, and proliferation. Experiment Overall Design: Scientific Approach: A7r5 rat embryonic vascular smooth muscle cells (VSMCs) (ATCC, CRL-1444) were infected for 72 hours with adenoviral vectors containing human GLUT1 or empty vector controls at a multiplicity of infection of 10 (MOI of 1 = 100 particles/cell) and grown in both high glucose (25mM) and low glucose (5.5mM) media. The human GLUT1 cDNA adenoviral vector and empty vector controls were a gift from Dr Arno Kumagai (University of Michigan). Total RNA was isolated using TRIzol (Invitrogen Life Technologies, Carlsbad, CA), followed by extraction with phenol/chloroform until the interface was clear. Total RNA was further purified using Qiagen RNeasy Mini Kit (Qiagen 74106). Immunoblot analysis was conducted to confirm GLUT1 overexpression at the time of Total RNA isolation (72 hours post-infection) for each condition. Experiment Overall Design: Number of chips: Total RNA was isolated from each of 2 conditions (control cells in low glucose (5.5mM), and GLUT1 overexpressing cells in low glucose), on three separate days and pooled to obtain one sample for each condition. In total we submitted two samples.
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Project description:We report RNA sequencing data from the postnatal cardiac myocytes of the wild type and Glucose transporter 1 (Glut1) overexpressed mouse
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Project description:Abstract: Therapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis. Tumor cells proximal to blood vessels instead express the lactate transporter MCT1, and p-S6, the latter reflecting mTOR signaling. Normoxic cancer cells import and metabolize lactate, resulting in upregulation of mTOR signaling via glutamine metabolism enhanced by lactate catabolism. Thus metabolic symbiosis is established in the face of angiogenesis inhibition, whereby hypoxic cancer cells import glucose and export lactate, while normoxic cells import and catabolize lactate. mTOR signaling inhibition disrupts this metabolic symbiosis, associated with upregulation of the glucose transporter GLUT2.
2016-07-15 | GSE80436 | GEO
Project description:Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins. Since these mutations do not affect protein structure, the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1 and CACNA1H) lead to an increased binding of clathrin. In all three cases, the mutation creates a dileucine motif known to mediate clathrin-dependent trafficking. Follow-up experiments on full length GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments in a model cell line and in patient-derived induced pluripotent stem cells. Mutant GLUT1 interacts with adaptor proteins (APs) in vitro, and knocking-down AP-2 reverts the cellular mislocalization. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in structurally disordered cytosolic domains of transmembrane proteins. Thus, several mutations in disordered regions appear to cause “dileucineopathies”.
2018-09-13 | PXD010027 | Pride
Project description:Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins. Since these mutations do not affect protein structure, the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1 and CACNA1H) lead to an increased binding of clathrin. In all three cases, the mutation creates a dileucine motif known to mediate clathrin-dependent trafficking. Follow-up experiments on full length GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments in a model cell line and in patient-derived induced pluripotent stem cells. Mutant GLUT1 interacts with adaptor proteins (APs) in vitro, and knocking-down AP-2 reverts the cellular mislocalization. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in structurally disordered cytosolic domains of transmembrane proteins. Thus, several mutations in disordered regions appear to cause “dileucineopathies”.
2018-09-13 | PXD010061 | Pride
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138753 | GEO
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138756 | GEO