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GSE87830
Homo sapiens
256 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 94 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The 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.
Publication Title
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The 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.
Publication Title
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression. ECV304 endothelial cells were stimulated with IL-1 100 U/ml in the presence or absence of Aminaphtone 6 g/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray.
Publication Title
Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple myeloma (MM)-induced osteoclast (OC) formation occurs in close contact with MM cell infiltration into the bone marrow (BM) due to the imbalance of the receptor activator of NF-kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio in favor of RANKL in the micorenvironment. Soluble factors including CCL3/MIP-1?, IL7 and IL-3 also contribute to the increased OC formation in MM.The immunomodulatory drugs (IMiDs) directly inhibit OCs, however their effect on the mechanisms involved in MM-induced OC formation are not known and have been investigated in this study. We found that both Lenalidomide (LEN) and Pomalidomide (POM), at concentration ranging reached in vivo, significantly blunted RANKL up-regulation normalizing the RANKL/OPG ratio in human BM osteoprogenitor cells (PreOBs) co-cultured with MM cells and inhibited CCL3/MIP-1? production by MM cells. The reduction of CD49d expression on MM cells, a molecule critically involved in RANKL up-regulation in the micorenvironment, accompanied this effect. Consistently the pro-osteoclastogenic property of the conditioned medium of MM cells co-cultured with PreOBs was reduced in the presence of both IMiDs. By microarray analysis we further investigated the effect of POM and LEN on the transcriptional profile of both MM cells and PreOBs. We found a significant down-regulation in MM cells, in addition to CD49d, of genes belonging to the adhesion molecules family such as ITGA8 and ICAM2 (CD102) induced by both IMiDs compounds. In conclusion our data suggest that POM and LEN inhibits MM-induced OC formation through the inhibition of RANKL/OPG ratio targeting the expression of adhesion molecules by MM cells.
Publication Title
Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Karyotypic instability, including numerical and structural chromosomal aberrations, represents a distinct feature of multiple myeloma (MM). 40-50% of patients displayed hyperdiploidy, defined by recurrent trisomies of non-random chromosomes. To characterize hyperdiploid (H) and nonhyperdiploid (NH) MM molecularly, we analyzed the gene expression profiles of 66 primary tumors, and used FISH to investigate the major chromosomal alterations. The differential expression of 225 genes mainly involved in protein biosynthesis, transcriptional machinery and oxidative phosphorylation distinguished the 28 H-MM from the 38 NH-MM cases. The 204 upregulated genes in H-MM mapped mainly to the chromosomes involved in hyperdiploidy, and the29% up-regulated genes in NH-MM mapped to 16q. The identified transcriptional fingerprint was robustly validated on a publicly available gene expression dataset of 64 MM cases; and the global expression modulation of regions on the chromosomes involved in hyperdiploidy was verified using a self-developed non-parametric statistical method. We showed that H-MM could be further divided into two distinct molecular and transcriptional entities, characterized by the presence of trisomy 11 and 1q-extracopies/chromosome 13 deletion, respectively. Our data reinforce the importance of combining molecular cytogenetics and gene expression profiling to define a genomic framework for the study of MM pathogenesis and clinical management.
Publication Title
Upregulation of translational machinery and distinct genetic subgroups characterise hyperdiploidy in multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic disease, diabetes, infertility and cancer. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 253 differentially modulated probe sets, identifying 217 well-characterized genes. A large part of these were associated with cell adhesion and/or angiogenesis and with transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway, were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems.
Publication Title
Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 158 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Mapping 50K Xba240 SNP Array (mapping50kxba240)
Description
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide dosage effect on gene and microRNA expression
Publication Title
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 158 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Multiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM.
Publication Title
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias.
Publication Title
The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples