Background. Although the emergence of RNA sequencing (RNA-seq), microarrays remain in widespread use for gene expression analysis in the clinic. There are over 767,000 RNA microarrays from human samples in public repositories, which are an invaluable resource for biomedical research and personalized medicine. The absolute gene expression analysis allows the transcriptome profiling of all expressed genes under the specific biological condition without the need of a reference sample. However, the background fluorescence represents a challenge to determine the absolute gene expression in microarrays. Given that the Y chromosome is absent in female subjects, we used it as a new approach for absolute gene expression analysis in which the fluorescence of the Y chromosome genes of female subjects was used as the background fluorescence for all the probes in the microarray. This fluorescence was used to establish an absolute gene expression threshold, allowing the differentiation between expressed and non-expressed genes in microarrays.
A novel approach for human whole transcriptome analysis based on absolute gene expression of microarray data.
Sex, Specimen part
View SamplesThe guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played non redundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factorb family ligand inhibin bA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells.
Cell line
View SamplesIntroduction: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH. Methods: Fasting plasma for determination of lipid profiles, inflammatory molecules, and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene expression profile was analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. Results: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared to controls. Atorvastatin treatment modified the expression of 87 genes. Changes in the expression of some genes, confirmed by real time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen tumor necrosis factor receptor superfamily, member 25 and CD96) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. Conclusions: Our results demonstrate clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.
Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.
No sample metadata fields
View SamplesIn this study we analyzed the behavior of bone marrow MSC (BM-MSC) from MPN patients with the mutation in JAK2V617F. We initially characterized the biological function and gene expression profile changes in BM-MSC from MPN patients when compared to BM-MSC of healthy donors (HD). Then, we established co-cultures between MSC cell lines (HTERT and HS5) and the UKE-1 MPN cell line, and performed RT-PCR to study if the leukemic cells were able to modify the genes related to hematopoietic support.
Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis.
Specimen part, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe analysed the RNA profile of IPSC-derived dopaminergic neurons from idiophatic and genetic form (LRRK2) of Parkinsons disease (PD). Both, idiopathic and genetic form of the disease show similar expression alterations and were merged in one whole PD group. We found 437 differentially expressed genes (DEGs) in the PD group as a whole. Up-regulated DEGs (n=254) encompassed genes involved in neural functions and transcription factor functions whereas down-regulated DEGs (n=183) affected basic homeostasis. These data point towards the presence of gene - and also protein - expression changes in DAn from PD patients which co-occur simultaneously along with DNA methylation changes.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage
View SamplesNeuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Cell line
View SamplesCamptothecin (CPT) is a plant alkaloid that specifically binds topoisomerase I (Topo I) inhibiting its activity and inducing double stranded breaks in the DNA, activating the genotoxic cell responses, and ultimately, it might trigger programmed cell death (PCD). We used microarrays to detail the changes in gene expression during as a consequence of CPT treatment in maize immature embryos. In four independent experiments immature embryos were plated on MS medium supplemented with 50 uM CPT and incubated during three days. Untreated embryos incubated on MS medium were used as controls.
Transcriptomic and proteomic profiling of maize embryos exposed to camptothecin.
Specimen part, Compound
View SamplesBackground: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells.
Long-term reduction of T-cell intracellular antigens reveals a transcriptome associated with extracellular matrix and cell adhesion components.
Cell line
View SamplesThe identification of new agents that may modulate the progression of cancer cell growth is of great interest. In this regard, dietary agents can be utilized to identify molecular targets to be used as part of a chemopreventive strategy. Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). We performed a genomic analysis to study the effect of UA on androgen-dependent LNCaP prostate adenocarcinoma cells. Cells were incubated with 40M UA for 24 hours, then, RNA was extracted. RNA samples were processed in the automated Biomek FX System (Beckman Coulter), where aRNA was produced, and labeled with Biotin, purified , fragmented and hybridized onto HG U219-24 Array, using the GeneChip HT 3IVT Express Kit . Afterwards, the GeneTitan Multi-Channel (MC) Instrument (Affymetrix) was used to hybridize, wash , stain , and scan the arrays. Microarray results were analyzed using the GeneSpring GX v13.0 software.
Urolithin A causes p21 up-regulation in prostate cancer cells.
Specimen part, Cell line
View Samples