Malignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Overall design: Transcriptomic analysis of two different stages of gliomagenesis
Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.
Specimen part, Cell line, Subject
View SamplesThe rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sex, Specimen part, Treatment, Subject
View SamplesWe devised a novel insertional mutagenesis approach based on lentiviral vectors to induce hepatocellular carcinoma in three mouse models and identified four novel cancer initiating genes. Two genes are the well characterized Braf and Sos1, while the other two are Fign, encoding an AAA ATPase whose functions are poorly understood, and the complex Dlk1-Dio3 imprinted region which has been recently implicated in cancer and stemness. Activation of Fign or Braf and upregulation of the Dlk1-Dio3 imprinted region are functionally interconnected and may altogether control cell transformation, stemness and energy metabolism. Moreover, all the genes identified play a relevant role in human hepatocarcinogenesis as their expression levels and/or transcriptional signatures induced by their deregulation predict a different clinical outcome in hepatocellular carcinoma patients. These series consists of mRNA expression microarray data (The GeneChip Mouse Gene 1.0 ST Array, Affymetrix) from 8 non-tumoral liver and 21 hepatocellular carcinoma induced by insertional mutagenesis.
Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer.
Specimen part
View SamplesTo investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesGastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed.
Genome-wide expression profile of sporadic gastric cancers with microsatellite instability.
No sample metadata fields
View SamplesGRN163L is a potent and specifictelomeraseinhibitor and in clinical trials for cancer treatment. To identify the biomarker that might predict response to telomease based therapy, gene expression analysis of the cancer cell lines after treatiment with telomerase inhibitor Imetelstat (GRN163L) was performed.
Interleukin 8 is a biomarker of telomerase inhibition in cancer cells.
Cell line
View SamplesEffect of SHMT1 knockdown on ovarian cancer tumor growth was analyzed
Serine hydroxymethyl transferase 1 stimulates pro-oncogenic cytokine expression through sialic acid to promote ovarian cancer tumor growth and progression.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View SamplesSF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed. NRSF/REST is a transcriptional repressor that represses expression of neuronal genes in non-neural tissues. Some data suggest that SF-1 and NRSF/REST can functionally interact in adrenocortical cancer cells.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View SamplesSF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View Samples