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GSE77230
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- 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- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
We assayed the effect of c-Jun overexpression on gene expression in the three DDLPS cell lines using RNA-Seq (Illumina). Overall design: 141, LPS12 and 510 has been overexpressed with c-Jun or control c-DNA and results were analyzed in high-througput sequencing metadata.
Publication Title
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Sample Metadata Fields
No sample metadata fields
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- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression (mRNA profiling) of U2OS osteosarcoma cells treated with 1 mM of the CDK4/6-specific inhibitor, PD0332991, versus vehicle (DMSO) for 4 hours
Publication Title
A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2500
Description
We performed a genome-scale CRISPR screen in a KRAS-mutant pancreatic cancer cell line treated with the MEK inhibitor trametinib, and found that loss of the transcriptional repressor CIC confers resistance to MEK inhibition. We determined that CIC loss also confers resistance to MEK or BRAF inhibition in lung cancer, colorectal cancer, and melanoma cell lines with mutant RAS or BRAF. CIC is a transcriptional repressor that is phosphorylated and inhibited by the MAPK pathway. We hypothesized that inhibition of the MAPK pathway would lead to activation of CIC and repression of CIC target genes. Loss of CIC would therefore restore expression of these genes, conferring drug resistance. To identify the relevant CIC target genes that mediate trametinib resistace, we generated 4 Cas9-expressing cell lines from different lineages and with different RAS or RAF mutations, and generated control (gGFP) or CIC-knockout (gCIC) cell lines. We treated cells with DMSO or trametinib for 24 hours, and performed NRA-seq. We found that trametinib treatment reduces expression of at least one member of the PEA3 family of ETS transcription factors (ETV1, ETV4, and ETV5) in all cell lines assessed, and that loss of CIC results in maintained expression of these genes despite MEK inhibition. We further validated that ETV1, 4, and 5 expression was necessary for resistance mediated by CIC loss; and that ETV1, 4, or 5 expression was sufficient to confer trametinib resistance. Overall design: 4 Cas9-expressing human cancer cell lines (A549, CALU1, HCT116, PATU8902) were used to generate 3 isogenic cell lines with intact CIC (gGFP-1) or knocked out CIC (gCIC-1 or gCIC-2). Each of these 12 cell lines were treated with DMSO or trametinib for 24 hours (duplicates)
Publication Title
ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The requirement for cyclin D function in tumor maintenance.
Sample Metadata Fields
Specimen part, Cell line
View Samples