Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA240061 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ras-related associated with diabetes (RRAD) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras regulated-transcriptome and epigenome were profiled by comparing T29H (a RasV12-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through Reduced representation bisulfite sequencing (RRBS-seq) and Digital gene expression (DGE) . We found that RasV12-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine (5-aza-dC) resulted in demethylation in RRAD promoter and restored RRAD expression in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting RRAD is a tumor suppressor gene. Our results indicate that RasV12-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis DGE-seq data for two cell lines (T29 and T29H) by were generated by deep sequencing using Illumina GAIIx.
2014-08-21 | E-GEOD-55567 | biostudies-arrayexpress
Project description:Ras-related associated with diabetes (RRAD) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras regulated-transcriptome and epigenome were profiled by comparing T29H (a RasV12-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through Reduced representation bisulfite sequencing (RRBS-seq) and Digital gene expression (DGE) . We found that RasV12-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2M-bM-^@M-2-deoxycytidine (5-aza-dC) resulted in demethylation in RRAD promoter and restored RRAD expression in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting RRAD is a tumor suppressor gene. Our results indicate that RasV12-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis Reduced representation bisulfite sequencing (MspI,~40-220bp size fraction) data for two cell lines (T29 and T29H) were generated by deep sequencing, in two replicates, using Illumina HiSeq 2000.
2014-08-21 | E-GEOD-55566 | biostudies-arrayexpress
Project description:Ras-related associated with diabetes (RRAD) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras regulated-transcriptome and epigenome were profiled by comparing T29H (a RasV12-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through Reduced representation bisulfite sequencing (RRBS-seq) and Digital gene expression (DGE) . We found that RasV12-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) resulted in demethylation in RRAD promoter and restored RRAD expression in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting RRAD is a tumor suppressor gene. Our results indicate that RasV12-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis
2014-08-21 | GSE55567 | GEO
Project description:Ras-related associated with diabetes (RRAD) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras regulated-transcriptome and epigenome were profiled by comparing T29H (a RasV12-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through Reduced representation bisulfite sequencing (RRBS-seq) and Digital gene expression (DGE) . We found that RasV12-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) resulted in demethylation in RRAD promoter and restored RRAD expression in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting RRAD is a tumor suppressor gene. Our results indicate that RasV12-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis
2014-08-21 | GSE55566 | GEO
Project description:Ras-induced epigenetic inactivation of RRAD promotes glucose uptake in a human ovarian cancer model
| PRJNA240059 | ENA
Project description:Ras-induced epigenetic inactivation of RRAD promotes glucose uptake in a human ovarian cancer model (RRBS-Seq]
| PRJNA240062 | ENA
Project description:We performed expression profiling on micro-dissected lung tumors derived from a doxycycline-inducible K-RAS mouse model in order to gain mechanistic insight into K-RAS-mediated tumor maintenance. In this model, the tumors were induced with doxycycline for 11 weeks (in order to obtain lung tumors). At this point the doxycyline was withrawn from the food of the mice and consequently K-RAS inactivated. Thus, the genome-wide analysis was performed on tumors at timepoints 0, 24h and 48h after K-RAS inactivation. Total RNA obtained from mouse lung tumors at time 0 and 24h or 48h after K-RAS inactivation.
2012-09-06 | E-GEOD-40606 | biostudies-arrayexpress
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146108 | GEO
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146107 | GEO
Project description:We used a positron emission tomography (PET) tracer 18F fluorodeoxyglucose ([18F]-FDG) and transcriptomic analysis to detect glucose uptake by cells in the bone marrow micro-environment with an MLL-AF9-induced mouse model. Leukaemic cells had the greatest glucose uptake. To determine whether glucose uptake is driven by intrinsic demand, we applied RNA-seq of sorted leukaemia cells (GFP+) and bone marrow micro-environment myeloid cells (GFP-CD11b+) from the MLL-AF9 transduced mouse model.
2023-04-14 | GSE227581 | GEO