RNA-seq of bone marrow CD34+ cells of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients to identify at the molecular pathways involved in primary resistance to AZA therapy. Overall design: RNA-seq of bone marrow CD34+ cells of MDS and CMML patients at pre-treatment and after 6 cycles of AZA treatment to identify at the molecular pathways involved in resistance to AZA therapy.
Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes.
No sample metadata fields
View SamplesThe aim of the study was to evaluate cocaine-induced changes in gene expression in a dopaminergic model.
Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence.
Cell line, Treatment
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In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesThe identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNAs (ceRNAs) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent. Herein, we investigated in silico the lncRNA and miRNA relationship in a representative datasets encompassing 95 MM and 30 plasma cell leukemia patients at diagnosis and in four normal controls, whose expression profiles were generated by a custom annotation pipeline to detect specific lncRNAs. We applied target prediction analysis based on miRanda and RNA22 algorithms to 235 lncRNAs and 459 miRNAs selected with a potential pivotal role in the pathology of MM. Among pairs that showed significant correlation between lncRNA and miRNA expression levels, we identified 10 lncRNA-miRNA relationships suggestive of novel ceRNA network with relevance in MM.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesThe identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNAs (ceRNAs) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent. Herein, we investigated in silico the lncRNA and miRNA relationship in a representative datasets encompassing 95 MM and 30 plasma cell leukemia patients at diagnosis and in four normal controls, whose expression profiles were generated by a custom annotation pipeline to detect specific lncRNAs. We applied target prediction analysis based on miRanda and RNA22 algorithms to 235 lncRNAs and 459 miRNAs selected with a potential pivotal role in the pathology of MM. Among pairs that showed significant correlation between lncRNA and miRNA expression levels, we identified 10 lncRNA-miRNA relationships suggestive of novel ceRNA network with relevance in MM.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesA key event in the pathogenic process of prion diseases is the conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform (PrPSc). Mice lacking PrP are resistant to prion infection, and down-regulation of PrPC during prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPC during prion diseases. However, the silencing of a protein that is widely expressed throughout the CNS could be detrimental to brain homeostasis. The physiological role of PrPC remains still unclear, but several putative functions have been proposed. Among these, several lines of evidence support PrPC function in neuronal development and maintenance.
Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus.
Specimen part
View SamplesDownregulation of expression and activity levels of the astroglial glutamate transporter EAAT2 is thought to be implicated in motor neuron excitotoxicity in amyotrophic lateral sclerosis (ALS). We previously reported that EAAT2 is cleaved by caspase-3 at the cytosolic C-terminus domain, impairing the transport activity and generating a proteolytic fragment found to be SUMO1 conjugated (CTE-SUMO1). We show here that this fragment accumulates in the nucleus of spinal cord astrocytes in vivo throughout the disease stages of the SOD1-G93A mouse model of ALS. In vitro expression in spinal cord astrocytes of the C-terminus peptide of EAAT2 (CTE), which was artificially fused to SUMO1 (CTE-SUMO1fus) to mimic the endogenous SUMOylation reaction, recapitulates the nuclear accumulation of the fragment seen in vivo and causes caspase-3 activation and axonal growth impairment in motor neuron-derived NSC-34 cells and primary motor neurons co-cultured with CTE-SUMO1fus-expressing spinal cord astrocytes. This indicates that CTE-SUMO1fus could trigger non-cell autonomous mechanisms of neurodegeneration. Prolonged nuclear accumulation of CTE-SUMO1fus in astrocytes leads to their degeneration, although the time frame of the cell-autonomous toxicity is longer than the one for the indirect toxic effect on motor neurons. As more evidence on the implication of SUMO substrates in neurodegenerative diseases emerges, our observations strongly suggest that the nuclear accumulation in spinal cord astrocytes of a SUMOylated proteolytic fragment of the astroglial glutamate transporter EAAT2 could take part to the pathogenesis of ALS and suggest a novel, unconventional role for EAAT2 in motor neuron degeneration in ALS.
Motor neuron impairment mediated by a sumoylated fragment of the glial glutamate transporter EAAT2.
Specimen part
View SamplesThe regulation of necrotic death and its relevance in anti-cancer therapy are largely unknown. Here we have investigated the pro-apoptotic and pro-necrotic activities of two ubiquitin-proteasome system inhibitors (UPSIs): bortezomib and G5. The present study points out that the glioblastoma cell lines U87MG and T98G are useful models to study the susceptibility to apoptosis and necrosis in response to UPSIs. U87MG cells are resistant to apoptosis induced by bortezomib and G5 but susceptible to necrosis induced by G5. On the opposite T98G cells are susceptible to apoptosis induced by both inhibitors but show some resistance to G5-induced necrosis. By comparing the transcriptional profiles of the two cell lines, we have found that the resistance to G5-induced necrosis could arise from differences in glutathione synthesis/utilization and in the microenvironment. In particular collagen IV, which is highly expressed in T98G cells, and fibronectin, whose adhesive function is counteracted by tenascin-C in U87MG cells, can restrain the necrotic response to G5. Collectively, our results provide an initial characterization of the molecular signals governing cell death by necrosis in glioblastoma cell lines.
Characterization of caspase-dependent and caspase-independent deaths in glioblastoma cells treated with inhibitors of the ubiquitin-proteasome system.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesAlloplasmic lines provide a unique tool to study the nucleo-cytoplasmic interactions. Alloplasmic lines T183 and T195 were developed through the introgression of the cytoplasm from Aegilops uniaristata (T183) and Aegilops squarrosa (T195) in the nuclear background of Triticum aestivum cv. Chris. Alloplasmic line TH237 was produced introgressing the Hordeum chilense accession H7 cytoplasm into the nuclear background of Triticum aestivum accession T20. Fifty seeds for each sample in pots of 11 cm diameter and grown in controlled conditions under 600E m-2 s1 high light intensity in a daily regime of 12 h light at 22C and 12 h darkness at 15C. Plants were bulked from each pot and three biological replicate used for the transcriptomics Fully expanded second leaves were collected two weeks from sowing in the middle of the light period and used for transcriptomic analysis.
Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations.
Specimen part
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