This SuperSeries is composed of the SubSeries listed below.
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions.
Cell line
View SamplesMultiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite current progress in improving patient outcome, MM remains largely incurable. Disease clonal and interpatient heterogeneity has hampered identification of a common underlying mechanism for disease establishment and have slowed the development of novel targeted therapies. Epigenetic aberrations are now emerging as increasingly important in tumorigenesis, thus selective targeting of crucial epigenetic enzymes may provide new therapeutic potential in cancer including MM. Recently, we and others suggested the histone methyltransferase enhancer of zeste homolog 2 (EZH2), to be a potential therapeutic target in MM. Now we show that pharmacological inhibition of EZH2 suppresses the MM cell growth through downregulation of MM-associated oncogenes; IRF-4, XBP-1, PRDM1/BLIMP-1and c-MYC. We also show that downregulation of these genes is mediated via reactivated expression of microRNAs with tumor suppressor functions; primarily miR125a-3p and miR320c. Using chromatin immunoprecipitation (ChIP) we demonstrate that miR125a-3p and miR320c are targets of EZH2 and H3K27me3 in MM cell lines and primary MM cells. Our results further highlight the importance of polycomb-mediated silencing in MM to include microRNAs with tumor suppressor activity. This novel role further strengthens the oncogenic features of EZH2 and its potential as a therapeutic target in MM.
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions.
Cell line
View SamplesAffymetrix Human Genome U133A platform was used to obtain gene expression profiles of 28 pathologically and clinically well characterized adenocarcinomas of the lung. In addition, EGFR status was determined by fluorescent in situ hybridization and immunohistochemistry.
Gene expression profiles of lung adenocarcinoma linked to histopathological grading and survival but not to EGF-R status: a microarray study.
Specimen part
View SamplesBackground:
Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation.
Specimen part
View SamplesMechanisms controlling the proliferative activity of neural stem/progenitor cells (NSPCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of FASN in NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for FASN to fuel lipogenesis. Thus, we here identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.
Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis.
Specimen part
View SamplesAnalysis of gene expression profile in peritoneal macrophage extracted from LPS or PBS challenged DUSP3-/- and WT mice. DUSP3 deletion protects mice from sepsis and endotoxemia. We performed a microarray analysis to get insights into the differentially regulated pathways between WT and KO under inflammatory conditions.
DUSP3 Genetic Deletion Confers M2-like Macrophage-Dependent Tolerance to Septic Shock.
Sex, Age, Specimen part
View SamplesWe examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression at baseline, without pro-inflammatory activation, in macrophages.
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
No sample metadata fields
View SamplesWe examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression underlying pro-inflammatory activation of macrophage.
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Specimen part
View SamplesInterrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength-specific, and dose- and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a polyethylene glycol matrix, hydrogel materials responsive to light in the cell-compatible red/far-red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechano-signaling pathways respond to changing mechanical environments, and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows addressing fundamental questions of how cells react to dynamic mechanical environments. Further, remote control of such matrices could create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. Overall design: Analysis of global gene expression changes due to differences in the mechanical properties of the phytochrome-based hydrogels
Phytochrome-Based Extracellular Matrix with Reversibly Tunable Mechanical Properties.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sex, Age, Race, Subject
View Samples