The overall aim of the present work was to identify MTG16 functions in leukemia cells. Alterations in quantity of the MTG16 co-repressor might affect gene regulation and cell metabolism in malignant cells. Differentiated cells secure energy for cellular homeostasis largely by mitochondrial oxidation. Whereas, mature cells, proliferating tumour cells including leukemia cells depend on glycolysis and mitochondrial respiration may be low even in oxygenrich environments.The same signal transduction pathways that govern cell proliferation give instructions for nutrient uptake and co-regulate metabolic processes. In this manner, the metabolism of tumor cells, and other highly proliferating cells, is adapted to stimulate anabolic glycolysisdriven processes for incorporation of nutrients into nucleotides, amino acids and lipids to synthesize macromolecules required for growth and proliferation.
The transcriptional co-repressor myeloid translocation gene 16 inhibits glycolysis and stimulates mitochondrial respiration.
Specimen part
View SamplesTo understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: Reconstitution of ELL2 expression in L363-ELL2-knockout cells
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression.
Specimen part, Disease, Disease stage, Cell line, Treatment, Subject
View SamplesTo understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: knock out ELL2 in L363 cells using CRISPR-Cas9
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression.
Disease, Disease stage, Cell line, Subject
View SamplesMicroarray based mRNA profiling was used to identify the mechanism of action for the small molecule VLX60.
Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity.
Cell line
View SamplesPrimary cultures of patient tumor cells (PCPTC) were used in a cell-based cytotoxicity screen. Microarray-based mRNA profiling was used to identify the mechanism-of-action for the small molecule VLX 50.
Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment.
Specimen part, Disease, Cell line, Treatment
View SamplesMicroarray based mRNA profiling was used to identify the mechanism of action for the small molecule VLX600.
Iron chelators target both proliferating and quiescent cancer cells.
Disease, Cell line, Treatment
View SamplesMicroarray based mRNA profiling was used to charactarize and compare the gene expression in cells grown as monolayer or spheroids.
Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
Cell line
View SamplesMicroarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out.
Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
Cell line, Treatment
View SamplesWe used high throughput sequencing to analyze the transcriptional profiling of EVT. By comparing the transcriptional profiling of EVT with or without H19 knockdown, numerous genes showed significantly altered expression as a result of H19 repression. Overall design: HTR cells were transfected with either control siRNA or siH19. 48h later after transfection, total RNA was extracted for library preparation and RNA-seq analysis to compare trancript profiles between siCon and siH19 cells.
H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction.
Cell line, Subject, Time
View SamplesPatients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFN which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
Sex, Age, Specimen part, Disease
View Samples