Filters
Technology
Platform
GSE14794
Homo sapiens
90 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
Background: 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.
Publication Title
Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 156 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 156 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We profiled gene expression from a stratified cohort of subjects to define influenza vaccine response in Young and Old
Publication Title
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Cyclins and cyclin-dependent kinases (CDKs) are hyperactivated in nearly all human tumor types. To identify new approaches for interfering with cyclins/CDKs, we systematically searched for microRNAs (miRNAs) regulating these proteins. We uncovered a group of miRNAs that target nearly all cyclins and CDKs, and demonstrated that these miRNAs are very effective in shutting off cancer cell expansion. By profiling the response of over 120 human cancer cell lines representing 12 tumor types to these cell-cycle-targeting miRNAs, we identified miRNAs particularly effective against triple-negative breast cancers and KRAS-mutated cancers. We also derived expression-based algorithm that predicts response of primary tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we halted tumor progression in seven mouse xenograft models, including three highly aggressive and treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell-cycle-targeting miRNAs for treatment of refractory cancer types. Overall design: RNA-seq for SW900 cells transfected with 25 nM of miR-193a-3p mimic or 25 nM of negative miRNA control (Negative control #2, Ambion).
Publication Title
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cyclins and cyclin-dependent kinases (CDKs) are hyperactivated in nearly all human tumor types. To identify new approaches for interfering with cyclins/CDKs, we systematically searched for microRNAs (miRNAs) regulating these proteins. We uncovered a group of miRNAs that target nearly all cyclins and CDKs, and demonstrated that these miRNAs are very effective in shutting off cancer cell expansion. By profiling the response of over 120 human cancer cell lines representing 12 tumor types to these cell-cycle-targeting miRNAs, we identified miRNAs particularly effective against triple-negative breast cancers and KRAS-mutated cancers. We also derived expression-based algorithm that predicts response of primary tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we halted tumor progression in seven mouse xenograft models, including three highly aggressive and treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell-cycle-targeting miRNAs for treatment of refractory cancer types.
Publication Title
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The retinoblastoma tumor suppressor protein (Rb) regulates early G1 phase checkpoints, including the DNA damage response, as well as cell cycle exit and differentiation. The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 partially inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, resulting in release of E2F transcription factors. However, this model remains largely unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is un-phosphorylated in G0 cells and becomes exclusively mono-phosphorylated throughout all of early G1 phase by cyclin D:Cdk4/6. Early G1 phase mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but each shows a preferential binding pattern to specific E2F1-4 transcription factors. At the late G1 Restriction Point, cyclin E:Cdk2 inactivates Rb by a quantum hyper-phosphorylation (>12 phosphates/Rb). Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription. In contrast, a non-phosphorylatable ?Cdk-Rb allele was non-functional for regulating a DNA damage response, but functional for driving cell cycle exit and differentiation during myogenesis. These observations fundamentally change our understanding of G1 cell cycle progression and show that there is no progressive multi-phosphorylation or hypo-phosphorylation inactivation of Rb during early G1 phase by cyclin D:Cdk4/6. Instead, cyclin D:Cdk4/6 generates functionally active, mono-phosphorylated Rb that is the only Rb isoform present in cells during early G1 phase.
Publication Title
Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem and progenitor cells are the critical units for tissue maintenance, regeneration, and repair. The activation of regenerative events in response to tissue injury has been correlated with mobilization of tissue-resident progenitor cells, which is functional to the wound healing process. However, until now there has been no evidence for the presence of cells with a healing capacity circulating in healthy conditions. We identified a rare cell population present in the peripheral blood of healthy mice that actively participates in tissue repair. These Circulating cells, with a Homing ability and involved in the Healing process (CH cells), were identified by an innovative flowcytometry strategy as small cells not expressing CD45 and lineage markers. Their transcriptome profile revealed that CH cells are unique and present a high expression of key pluripotency- and epiblast-associated genes. More importantly, CH-labeled cells derived from healthy Red Fluorescent Protein (RFP)-transgenic mice and systemically injected into syngeneic fractured wild-type mice migrated and engrafted in wounded tissues, ultimately differentiating into tissue-specific cells. Accordingly, the number of CH cells in the peripheral blood rapidly decreased following femoral fracture. These findings uncover the existence of constitutively circulating cells that may represent novel, accessible, and versatile effectors of therapeutic tissue regeneration.
Publication Title
Identification of a New Cell Population Constitutively Circulating in Healthy Conditions and Endowed with a Homing Ability Toward Injured Sites.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Affymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.
Publication Title
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Sample Metadata Fields
Specimen part, Cell line
View Samples