This SuperSeries is composed of the SubSeries listed below.
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Cell line
View SamplesThe multifunctional protein tyrosine phosphatase PRL-1 (Gene Symbol: PTP4A1) has been identified as an important oncogene with roles in promoting cell proliferation, survival, migration, invasion, and metastasis. However, little is currently known about the signaling pathways through which it mediates its effects.
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Cell line
View SamplesIn an effort to define unique and common signatures of NK cell activity that is non-detected at the protein level, we studied the entire transcriptome of NK cells.
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.
Specimen part, Treatment, Subject
View SamplesBackground: Prostate cancer (PC), a complex disease, can be relatively harmless or extremely aggressive. To identify candidate genes involved in causal pathways of aggressive PC, we implemented a systems biology approach by combining differential expression analysis and co-expression network analysis to evaluate transcriptional profiles using lymphoblastoid cell lines from 62 PC patients with aggressive phenotype (Gleason grade > 8) and 63 PC patients with nonaggressive phenotype (Gleason grade < 5). From 13935 mRNA genes and 273 microRNAs tested, we identified significant differences in 1100 mRNAs and 7 microRNAs with false discovery rate < 0.01. We also identified a co-expression module demonstrating significant association with the aggressive phenotype of PC (p=3.67x10-11). The module of interest was characterized by over-representation of cell cycle-related genes (false discovery rate = 3.50x10-50). From this module, we further defined 20 hub genes that were highly connected to other genes. Interestingly, five of the 7 differentially expressed microRNAs have been implicated in cell cycle regulation and two (miR-145 and miR-331-3p) are predicted to target three of the 20 hub genes. Ectopic expression of these two microRNAs reduced expression of target hub genes and subsequently resulted in cell growth inhibition and apoptosis. These results suggest that cell cycle is likely to be a molecular pathway causing aggressive phenotype of PC. Further characterization of cell cycle-related genes (particularly, the hub genes) and miRNAs that regulate these hub genes could facilitate identification of candidate genes responsible for the aggressive phenotype and lead to a better understanding of PC etiology and progression [Cancer Res 2009;69(24):94907].
Gene networks and microRNAs implicated in aggressive prostate cancer.
Cell line
View SamplesBackground: Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and use loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs. Methodology/Principal Findings: To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q <0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological pathways related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation. Surprisingly, most miRNA-correlated genes were not direct targets predicted by mRNA target prediction program, TargetScan, suggesting indirect endogenous relationship between miRNAs and their correlated mRNAs. Conclusions/Significance: This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.
Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines.
Cell line
View SamplesEukaryotic mRNAs undergo a cycle of transcription, nuclear export, and degradation. A major challenge is to obtain a global, quantitative view of these processes. Here we measured the genome-wide nucleocytoplasmic dynamics of mRNA in Drosophila cells by metabolic labeling in combination with cellular fractionation. By mathematical modeling of these data we determined rates of transcription, export and cytoplasmic decay for >5,000 genes. We characterized these kinetic rates and investigated links with mRNA features, RNA-binding proteins (RBPs) and chromatin states. We found prominent correlations between mRNA decay rate and transcript size, while nuclear export rates are linked to the size of the 3''UTR. Transcription, export and decay rates are each associated with distinct spectra of RBPs. Specific classes of genes, such as those encoding cytoplasmic ribosomal proteins, exhibit characteristic combinations of rate constants, suggesting modular control. Overall, transcription and decay rates have a major impact on transcript abundance, while nuclear export is of minor importance. Finally, correlations between rate constants suggest global coordination between the three processes. Our approach should be generally applicable to other cell systems and provides insights into the genome-wide nucleocytoplasmic kinetics of mRNA. Overall design: 24 RNA-seq experiments comprising 2 biological replicates: pre-exsiting nuclear mRNA time 0h (samples 1&13), pre-exsiting nuclear mRNA time 0.5h (samples 2&14), pre-exsiting nuclear mRNA time 1.5h (samples 3&15) , pre-exsiting nuclear mRNA time 3h (samples 4&16), pre-exsiting nuclear mRNA time 5h (samples 5&17), pre-exsiting nuclear mRNA time 7.5h (samples 6&18), pre-exsiting cytoplasmic mRNA time 0h (samples 7&19), pre-exsiting cytoplasmic mRNA time 0.5h (samples 8&20), pre-exsiting cytoplasmic mRNA time 1.5h (samples 9&21) , pre-exsiting cytoplasmic mRNA time 3h (samples 10&22), pre-exsiting cytoplasmic mRNA time 5h (samples 11&23), pre-exsiting cytoplasmic mRNA time 7.5h (samples 12&24)
Comprehensive analysis of nucleocytoplasmic dynamics of mRNA in Drosophila cells.
Cell line, Treatment, Subject
View SamplesIn mammals, the nuclear lamina interacts with hundreds of large genomic regions, termed lamina-associated domains (LADs) that are generally in a transcriptionally repressed state. Lamins form the major structural component of the lamina and have been reported to bind DNA and chromatin. Here we systematically evaluated whether lamins are necessary for the peripheral localization of LADs in murine embryonic stem cells. Surprisingly, removal of essentially all lamins did not have any detectable effect on the genome-wide interaction pattern of chromatin with the inner nuclear membrane. This suggests that other components of the inner nuclear membrane mediate these interactions. Overall design: 2 samples, each with a biological replicate: wt mESC, B type lamin null (dKO) dKO mESC
Nuclear lamins are not required for lamina-associated domain organization in mouse embryonic stem cells.
No sample metadata fields
View SamplesChanges in endothelial phenotype induced by E. coli-derived Shiga toxins (Stx) are believed to play a critical role in the pathogenesis of hemolytic uremic syndrome. Stx inactivate host ribosomes, but also alter gene expression at concentrations that minimally affect global protein synthesis. The effect of Stx on the gene expression profile of human microvascular endothelial cells was examined using the Affymetrix HG-U133A platform. Data were processed using 13 different methods and revealed 369 unique differentially expressed genes, 318 of which were up-regulated and 51 of which were down-regulated. These studies implicated activation of the CXCR4/CXCR7/SDF-1 chemokine pathway in Stx-mediated pathogenesis.
The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.
Sex
View SamplesAnalysis of the role of PARP1 in gene transcription in MCF7 cells under non-stress conditions. The hypothesis was that PARP1 activity in MCF7 cells plays a role in gene transcription. The results indicate that PARP1 inhibition does not significantly affect transcription after 6 hours of treatment.
Basal activity of a PARP1-NuA4 complex varies dramatically across cancer cell lines.
Specimen part, Cell line
View SamplesAnalysis of the role of PARP1 in gene transcription in cell lines with variable PARP1 activity.
Basal activity of a PARP1-NuA4 complex varies dramatically across cancer cell lines.
Specimen part, Cell line
View Samples