Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Ras-induced epigenetic inactivation of RRAD promotes glucose uptake in a human ovarian cancer model [DGE-Seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: mao biao

PROVIDER: E-GEOD-55567 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Ras-induced epigenetic inactivation of the RRAD (Ras-related associated with diabetes) gene promotes glucose uptake in a human ovarian cancer model.

Wang Yan Y Li Guiling G Mao Fengbiao F Li Xianfeng X Liu Qi Q Chen Lin L Lv Lu L Wang Xin X Wu Jinyu J Dai Wei W Wang Guan G Zhao Enfeng E Tang Kai-Fu KF Tang Kai-Fu KF Sun Zhong Sheng ZS

The Journal of biological chemistry 20140319 20

RRAD (Ras-related associated with diabetes) 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 Ras(V12)-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through r ...[more]

PMID: 24648519

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Dataset Information

Ras-induced epigenetic inactivation of RRAD promotes glucose uptake in a human ovarian cancer model [DGE-Seq]

Publications

Ras-induced epigenetic inactivation of the RRAD (Ras-related associated with diabetes) gene promotes glucose uptake in a human ovarian cancer model.

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