Glucocorticoids (GCs) are a central component in treating childhood acute lymphoblastic leukemia (chALL). They mainly act via regulating gene transcription. However, control of mRNA translation by GC has never been assessed systematically. In our research, T- and precursor B-ALL cells were cultured with and without GC for 6 hours and subjected to translational profiling, a technique combining sucrose gradient fractionation and microarray analysis of mRNA in different fractions. Analysis of GC regulation in different pools revealed no significant differences in regulation of mRNA translation by GC, suggesting no evidence for translational regulation by GC.
Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.
Cell line, Treatment
View SamplesDissection of melanoma heterogeneity through gene expression profiling has led to the identification of two major phenotypes, conventionally defined as MITF high / proliferative and AXL high / invasive. Tumors or single melanoma cells characterized by a predominant AXL-related gene program show enhanced expression of sets of genes involved in motility, invasion and regulation of epithelial-mesenchymal transition (EMT), while these genes are downregulated in tumors or cells with a predominant MITF-related gene program. The activation of the AXLhi/MITFlo invasive gene program in melanoma is characterized by aberrant expression of transcription factors (TFs) involved in the embryonic EMT process. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Here we provide evidence for a new actionable pathway that controls melanoma EMT-like/invasive phenotype. We show that in MITFlo melanomas, the TF NFATc2 controls the EMT-like transcriptional program, the invasive ability of neoplastic cells, as well as in-vitro and in-vivo growth, through a pathway that functionally links c-myc to FOXM1 and EZH2. Targeting of NFATc2, FOXM1 or EZH2 inhibited melanoma migratory and invasive activity. Moreover, pharmacological co-targeting of NFATc2 and EZH2 promoted apoptosis of BRAF-mutant melanomas with intrinsic resistance to BRAF inhibition.
An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesGene expression profiling of liver biopsies collected from 33 healthy liver donors ranging from 13 to 90 years old. The Affymetrix HG-U133 Plus 2.0 GeneChip platform was used to evaluate gene-expression.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesTherapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. A large panel of melanoma were characterized for resistance/susceptibility to different inhibitors targeting MAPK and PI3K/mTOR signaling pathways and the synergistic effect of combinatorial treatments affecting both pathways. These effects were evaluated in terms of cell viability (MTT), apoptosis (Annexin V-PI), caspase 3/7 activity and subG1 cell fraction, highlighting a hierarchy in the combination effects. Further, a smaller panel of melanoma cell lines, were treated with inhibitors singularly and in combination to test the effects on the expression of principal proteins involved in these two pathways. Gene expression profile was performed to analyse the gene modulation induced by inhibitors to identify new strategies to fight melanoma resistance.
Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade.
Specimen part, Cell line, Treatment
View SamplesThere is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma.
MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.
Specimen part
View SamplesTo identify RNA transcripts involved in acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing (RNA-seq) revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Overall design: Examination of transcriptomic response of human PTECs to hypoxic or inflammatory injury
The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury.
Specimen part, Treatment, Subject
View SamplesQuiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells.
Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Specimen part, Disease, Subject
View SamplesBackground: RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript. Results: Independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage. Conclusions: Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases. Overall design: Three independent samples of D. melanogaster female heads were collected with each sample representing a unique pool of biological material. Each sample was prepared according to manufacturer's instructions and then the same library was run on two lanes of a Solexa/Illumina flow cell, resulting in two technical replicates for each biological replicate, runs were 36 base-pair paired end.
A flexible Bayesian method for detecting allelic imbalance in RNA-seq data.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis.
Age, Specimen part, Disease, Disease stage
View Samples