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Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MicroRNAs have been demonstrated to be deregulated in multiple myeloma (MM). We have previously reported the downregulation of miR-214 in MM compared to normal plasma cells. In the present study, we have explored the functional role of miR-214 in myeloma pathogenesis. Ectopic expression of miR-214 reduced cell growth and induced apoptosis of myeloma cells. In order to identify the potential direct target genes of miR-214 which could be involved in the biological pathways regulated by this miRNA, gene expression profiling of H929 myeloma cell line transfected with precursor miR-214 was carried out. Functional analysis revealed significant enrichment for DNA replication, cell cycle phase and DNA binding. We show that miR-214 directly down-regulates the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-UTR. In addition, gankyrin inhibition induced an increase of P53 mRNA levels and subsequent up-regulation in CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53. In conclusion, we demonstrate that miR-214 function as a tumor suppressor in myeloma by a positive regulation of p53 and inhibition of DNA replication.
Publication Title
Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication.
Sample Metadata Fields
Cell line
View Samples
GSE16558- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Specific microRNA (miRNA) signatures have been associated with different cytogenetic subtypes in acute leukemias. This finding prompted us to investigate potential associations between genetic abnormalities in multiple myeloma (MM) and singular miRNA expression profiles. Moreover, global gene expression profiling was also analyzed to find correlated miRNA-gene expression and select miRNA target genes that show such correlation. For this purpose, we analyzed the expression level of 365 miRNAs and the gene expression profiling in sixty newly diagnosed MM patients, selected to represent the most relevant recurrent genetic abnormalities. Supervised analysis showed significantly deregulated miRNAs in the different cytogenetic subtypes as compared to normal PC. Interestingly, miR-1 and miR-133a clustered on the same chromosomal loci, were specifically overexpressed in the cases with t(14;16). The analysis of the relationship between miRNA expression and their respective target genes showed a conserved inverse correlation between several miRNAs deregulated in MM cells and CCND2 expression level. These results illustrate, for the first time, that miRNA expression pattern in MM is associated with genetic abnormalities, and that the correlation of the expression profile of miRNA and their putative mRNA targets is useful to find statistically significant protein-coding genes in MM pathogenesis associated to changes in specific miRNAs.
Publication Title
Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus, Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Kinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. Results: Filanesib showed in vitro and in vivo synergy with all IMiDs plus dexamethasone treatment, particularly with the pomalidomide combination (PDF). Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and it was shown to be mediated by impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, PDF increased the activation of the proapoptotic protein Bax, which has been previously associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Conclusions: Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone and es-tablished the basis for a recently activated trial being conducted by the Spanish MM group investigating this combination in relapsed MM patients.
Publication Title
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Kinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. Results: Filanesib showed in vitro and in vivo synergy with all IMiDs plus dexamethasone treatment, particularly with the pomalidomide combination (PDF). Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and it was shown to be mediated by impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, PDF increased the activation of the proapoptotic protein Bax, which has been previously associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Conclusions: Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone and es-tablished the basis for a recently activated trial being conducted by the Spanish MM group investigating this combination in relapsed MM patients.
Publication Title
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma - excessive ASM growth are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as interleukin 1beta and tumor necrosis factor alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and interleukin 1beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis.
Publication Title
Glucocorticoid- and protein kinase A-dependent transcriptome regulation in airway smooth muscle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Background: Macrophages are important cells in pathogenesis of obstructive lung diseases including asthma and chronic obstructive pulmonary disease (COPD). The aim of the study was a multivariate, genetic, comparative analysis of macrophages from patients with asthma and COPD.
Publication Title
Genetic characterization of macrophages from induced sputum of patients with asthma and chronic obstructive pulmonary disease.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
GEP on Affymetrix Genechip HTA 2.0 microarrays was performed on ex vivo cell-sorted GC-Tfh and pre-Tfh from TONS and FL
Publication Title
Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
GEP on Affymetrix U133+2.0 microarrays was performed on in vitro expanded stromal cells
Publication Title
Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
Illumina HiSeq 2000
Description
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene. FRDA patients have low FXN mRNA and frataxin protein levels when compared with heterozygous carriers or healthy controls. Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking. Peripheral tissues, including blood cells, buccal cells, and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis. However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided. Transcriptome profiling of FRDA skin fibroblasts revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins. Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in the FRDA cells. Finally, comparison of genes differentially expressed in FRDA fibroblasts to 3 previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes. Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. Overall design: We used RNA sequencing to profile the transcriptomes of primary fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals.
Publication Title
A Comprehensive Transcriptome Analysis Identifies FXN and BDNF as Novel Targets of miRNAs in Friedreich's Ataxia Patients.
Sample Metadata Fields
Specimen part, Subject
View Samples