2-Deoxyglucose induced transcription in control and MondoA knockdown cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE11242 | GEO | 2008/04/24
SECONDARY ACCESSION(S): PRJNA106745
REPOSITORIES: GEO
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Project description:To determine the contibution of the transcription factor MondoA to 2-deoxyglucose-induced transcription expression analysis was carried out in control and MondoA knockdown cells HA1ER cells are human embryonic kidney cells transformed with hTERT, SV40 Early region and activated H-Ras Keywords: cell type comparision, genetic modification HA1ER cells, Control (NS) or MondoA knockdown (M2), were starved for glucose overnight and then treated with 2-deoxyglucose for 3 hours
2008-04-24 | E-GEOD-11242 | biostudies-arrayexpress
Project description:The complexity and heterogeneity of cancer cells are under-represented by the current experimental models which revolve around primary tumor cells, cancer cell lines, and rodent models. We used the transformed cell model in our studies. IMR90 and BJ fibroblast cells were transformed by three oncogenic genetic factors, SV40 Large-T antigen, H-Ras and human telomerase (hTERT). These transformed cells can grow under anchorage independent conditions, are self-sufficient in growth signals, have decreased sensitivity to apoptosis, and showed recurrent chromosomal abnormalities. Further characterization of transformed cells through cell cycle profiling and mass spectrometry analysis also revealed an increased fraction in the G2/M phase, and an up-regulation of Ku70. Furthermore, transformed cells exhibited increased telomerase activity that was not accountable by hTERT overexpression alone. Microarray results revealed that hTERT overexpression promoted cell migration and the initiation of DNA damage responses; two cellular processes that are important in cancer progression. Collectively, these data imply that IMR90 transformed cell model is an invaluable tool for cancer studies. Our results in the systematic study of this model helped us identify possible early events in cancer transformation and reveal the extra-telomeric effects of telomerase in cell migration and DNA damage initiation. IMR90 and BJ fibroblast cells were transformed by three oncogenic genetic factors, SV40 Large-T antigen, H-Ras and human telomerase (hTERT). Through microarray analysis, gene expression of transformed cells were compared against control cells.
2010-12-31 | E-GEOD-24097 | biostudies-arrayexpress
Project description:The gene expression of two different tumorigenic human breast epithelial cell types (HMLER and BPLER) is compared with their immortalized parental cell-of-origin (HME and BPE). Experiment Overall Design: Two different normal primary human mammary epithelial cell populations (BPECs and HMECs) were isolated based on their differing in vitro growth requirements. These cells were immortalized by hTERT giving rise to BPE and HME cells. These hTERT immortalized cells (BPE and HME) were transformed by SV40-early region (LT+st) and H-Ras giving rise to transformed tumorigenic derivatives BPLER and HMLER. Biological replicates (4 - 6 samples) for each of 4 cell types were analyzed (untransformed hTERT immortalized cell populations (BPE&HME), and transformed tumorigenic derivatives (BPLER & HMLER).
2008-06-15 | E-GEOD-6885 | biostudies-arrayexpress
Project description:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted treatment of childhood ALL, we performed a comprehensive transcriptome analysis yielding a set of genes specifically overexpressed in ALL. Among them we identified MondoA - a transcription factor regulating glycolysis in response to glucose availability. Here, we confirm that MondoA is highly overexpressed ALL, whereas the MondoA paralog, MondoB, is not expressed. Expression studies revealed that MondoA is not regulated by glucose availability in leukemia cells, but by the presence of lactate. An in silico MondoA promoter analysis identified two methylation-prone CpG-islands and four conserved binding sites for runt-related transcription factor 1 (RUNX1). In fact, MondoA and RUNX1 are significantly coexpressed in leukemia and experimental blockage of DNA methylation leads to a further induction of MondoA. In addition, using microarray profiling, gene-set enrichment analysis and RNA interference we provide for the first time evidence that MondoA expression not only increases glucose catabolism, but also maintains a more immature ALL phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data hint to an important contribution of MondoA to leukemia aggressiveness validating MondoA as an attractive candidate for targeted treatment of ALL. Two nonsense shRNA expressing control Nalm6 clones and three MondoA shRNA expressing Nalm6 clones were subjected to microarray analysis.
2012-07-31 | E-GEOD-33967 | biostudies-arrayexpress
Project description:Human MondoA requires glucose as well as other modulatory signals to function in transcription. One such signal is acidosis, which increases MondoA activity and also drives a protective gene signature breast cancer. How low pH controls MondoA transcriptional activity is unknown. We found that low pH medium increases mitochondrial ATP (mtATP), which is subsequently exported from the mitochondrial matrix. Mitochondria-bound hexokinase transfers a phosphate from mtATP to cytoplasmic glucose to generate glucose-6-phosphate (G6P), which is an established MondoA activator. The outer mitochondrial membrane localization of MondoA suggests that it is positioned to coordinate the adaptive transcriptional response to a cell’s most abundant energy sources, cytoplasmic glucose and mtATP. In response to acidosis, MondoA shows preferential binding to just two targets, TXNIP and its paralog ARRDC4. Because these transcriptional targets are suppressors of glucose uptake we propose that MondoA is critical for restoring metabolic homeostasis in response to high energy charge.
2019-01-23 | GSE125089 | GEO
Project description:MondoA and its transcriptional target thioredoxin-interacting protein (TXNIP) constitute a regulatory loop that senses glycolytic flux and controls glucose availability. Cellular stress also triggers MondoA activity and TXNIP expression. To understand how MondoA integrates glucose and stress signals, we studied its activation by acidosis. We found that acidosis drives mitochondrial ATP (mtATP) synthesis. The subsequent export of mtATP from mitochondria via adenine-nucleotide transporter and voltage-dependent anion channel, and the enzymatic activity of mitochondria-bound hexokinase results in the production of glucose-6-phosphate (G6P), a known activator of MondoA transcriptional activity. MondoA localizes to the outer-mitochondrial membrane (OMM), and in response to G6P, shuttles to the nucleus and activates transcription. Our data suggests that MondoA is a required feature of a glucose- and mtATP-dependent, OMM-localized signaling center. We propose MondoA functions as a coincidence detector and its ability to sense glucose and cellular stress is coupled to the concerted production of G6P.
2019-01-23 | GSE117622 | GEO
Project description:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted treatment of childhood ALL, we performed a comprehensive transcriptome analysis yielding a set of genes specifically overexpressed in ALL. Among them we identified MondoA - a transcription factor regulating glycolysis in response to glucose availability. Here, we confirm that MondoA is highly overexpressed ALL, whereas the MondoA paralog, MondoB, is not expressed. Expression studies revealed that MondoA is not regulated by glucose availability in leukemia cells, but by the presence of lactate. An in silico MondoA promoter analysis identified two methylation-prone CpG-islands and four conserved binding sites for runt-related transcription factor 1 (RUNX1). In fact, MondoA and RUNX1 are significantly coexpressed in leukemia and experimental blockage of DNA methylation leads to a further induction of MondoA. In addition, using microarray profiling, gene-set enrichment analysis and RNA interference we provide for the first time evidence that MondoA expression not only increases glucose catabolism, but also maintains a more immature ALL phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data hint to an important contribution of MondoA to leukemia aggressiveness validating MondoA as an attractive candidate for targeted treatment of ALL.
2012-08-01 | GSE33967 | GEO
Project description:The complexity and heterogeneity of cancer cells are under-represented by the current experimental models which revolve around primary tumor cells, cancer cell lines, and rodent models. We used the transformed cell model in our studies. IMR90 and BJ fibroblast cells were transformed by three oncogenic genetic factors, SV40 Large-T antigen, H-Ras and human telomerase (hTERT). These transformed cells can grow under anchorage independent conditions, are self-sufficient in growth signals, have decreased sensitivity to apoptosis, and showed recurrent chromosomal abnormalities. Further characterization of transformed cells through cell cycle profiling and mass spectrometry analysis also revealed an increased fraction in the G2/M phase, and an up-regulation of Ku70. Furthermore, transformed cells exhibited increased telomerase activity that was not accountable by hTERT overexpression alone. Microarray results revealed that hTERT overexpression promoted cell migration and the initiation of DNA damage responses; two cellular processes that are important in cancer progression. Collectively, these data imply that IMR90 transformed cell model is an invaluable tool for cancer studies. Our results in the systematic study of this model helped us identify possible early events in cancer transformation and reveal the extra-telomeric effects of telomerase in cell migration and DNA damage initiation.
2010-12-31 | GSE24097 | GEO
Project description:In order to investigate the effect of MondoA loss on the expression of Myc-dependent genes, we performed a microarray analysis from RNAs isolated from TET21N cells expressing either control (siControl) or MondoA (siMondoA) siRNAs either with (NT) or without (Doxy) induced N-Myc expression. TET21N cells were grown in medium with either Doxy (Myc-Off) or No Treatment (Myc-On), then transiently transfected with either non-specific siRNA or MondoA siRNA in replicates. Cells were then lysed and RNA isolated.
2015-01-01 | E-GEOD-55538 | biostudies-arrayexpress
Project description:To identify miRNAs involved in ST-induced cell transformation, we used microarray chips containing 856 miRNA probes to define miRNA expression profiles in 16HBE,16HBER and 16HBERST cells. we created HBE cells at different stages of the cell transformation process (Pang et al., 2008). In brief, primary human bronchial epithelial cells were immortalized by expressing SV40 LT and hTERT (named as HBELH cells). HBER cells were created by introduction of an oncogenic version of H-Ras into HBELH cells. In agreement with previous studies, the expression of the oncogene H-Ras led to an increase in cell proliferation; however these cells (HBER) were unable to grow in soft agar or form tumors in immunodeficient mice. Subsequently, HBERST cells generated by the additional introduction of SV40 ST into HBER cells grew in an anchorage independent fashion and formed tumors in immunodeficient mice. Therefore, these cell lines represent distinct stages of immortalized cells (HBELH), pre-transformed cells (HBER) and transformed cells (HBERST). And then, the different miRNA expression profiles of HBE cells at different stages were assayed by miRNA microarray.
2011-04-01 | E-GEOD-26166 | biostudies-arrayexpress