Project description:This SuperSeries is composed of the following subset Series: GSE22866: DNA Methylation Profiling of Glioblastoma: Impact on Gene Expression and Clinical Outcome (Agilent Expression Study) GSE22867: DNA Methylation Profiling of Glioblastoma: Impact on Gene Expression and Clinical Outcome (Illumina) Refer to individual Series
Project description:Transcription profiling of muscles from mice with genetically modified muscle glycogen content to study the impact of glycogen content on gene expression.
Project description:Transcription profiling by array of rat normal bronchial epithelial cells to study the impact of TNFa on NFkB translocation and gene expression pattern
Project description:Glioblastoma is the most common malignant primary brain tumor. Clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNA (lncRNA) alterations may contribute to glioblastoma pathogenesis and potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was analyzed in multiple glioblastoma gene expression data sets for associations with prognosis and IDH mutation and MGMT promoter methylation status. The role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, less invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses and determination of reactive oxygen species (ROS) levels revealed impaired mitochondrial function and increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2) as a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.
Project description:We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize the management of glioblastoma (GBM) patients. We identified a novel six-CpGs signature that predicts the clinical outcome in GBM. The methylation profiling of 79 GBM patients has been used as a validation cohort to demonstrate the performance and the robustness of the identified six-CpGs signature. The status of the âMGMTâ biomarker, traditionally used by clinicians to predict survival in GBM, is also indicated per sample.