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SRP152886
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
p21-activated kinases (Paks) play an important role in oncogenic signaling pathways, and have therefore been considered as potential therapeutic targets in various cancers. Most studies of Pak function employ loss of function methods such as gene knock-out or knock-down, but these approaches result in loss of both the enzymatic and scaffolding properties of these proteins, and thus may not reflect the effects of small molecule inhibitors that block catalytic function. In this study we use a new transgenic mouse model in which a specific peptide inhibitor of Group I Paks (Pak1, -2, and -3) is conditionally expressed in response to Cre recombinase. Using this model, we show that inhibition of endogenous Pak function impedes the transition of adenoma to carcinoma in an Apc-driven mouse model of colorectal cancer. These effects are mediated by inhibition of Wnt signaling through reduced ß-catenin activity as well as suppression of an epithelial-mesenchymal transition program mediated by miR-200 and Snai1. These results highlight the potential therapeutic role of Pak1 inhibitors in colorectal cancer and suggest new therapeutic strategies in this disease. Overall design: We generated a targeted transgenic mouse carrying a conditionally activated PID allele at the Rosa26 locus, and showed that expression of this allele effectively inhibited the activity of Group I Paks in vivo. To assess the global molecular effects of Pak inhibition in Apc-null CRC cells, we next explored the effect of repressing Pak activity on transcription. Total RNA was extracted from PID+ and PID- cells and RNA-sequencing was preformed, followed by pathway analysis and qPCR validation for selected mRNAs.
Publication Title
Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer.
Sample Metadata Fields
Treatment, Subject
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The goal of this gene expression profiling experiment was to identify the entire set of transcription factors expressed during late pupal wing development (~80h APF) when pigmentation genes are expressed
Publication Title
Emergence and diversification of fly pigmentation through evolution of a gene regulatory module.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.1 ST Array (drogene11st)
Description
Analysis of Drosophila melanogaster early embryos (pre-zygotic genome activation) following the germ line-specific depletion of the dMLL3/4 histone methyltransferase (also known as Trr). These results provide insight into the molecular mechanisms responsible for the assembly of the zygotic genome at fertilization.
Publication Title
The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
As recently reported by our group, we performed miRNA and gene expression profiling of CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 42 PMF patient samples compared with 31 healthy controls. Integrative analysis of these profiles by means of Ingenuity Pathway Analysis (IPA) allowed the identification of several aberrantly regulated miRNA-mRNA target pairs organized in interaction networks. In particular, our results highlighted the up-regulation of miR-494-3p in CD34+ cells from PMF patients (Norfo R et al, Blood, 2014). Interestingly, among the most upregulated miRNAs, miR-494-3p emerges as being associated to the highest number of downregulated target mRNAs. In order to understand the biological role of miR-494-3p during the hematopoietic commitment and differentiation, we overexpressed this miRNA in cord blood (CB) derived-CD34+ cells. Cells were electroporated with either miR-494-3p miRNA mimic (mimic miR-494) or a negative control mimic (mimic Neg CTR). qRT-PCR confirmed miR-494-3p overexpression 24h and 4 days after transfection (RQ SEM, 512.60 137.37, p<.01, and 20.63 3.03, p<.01, respectively).
Publication Title
miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis hematopoietic stem/progenitor cells by targeting SOCS6.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lipid Nanoparticle-Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
To functionally characterize the role of miR-17 family in HCC, lentiviral vector-based miR inhibitor TuD was used to inhibit miR-17 family of microRNAs in HepG2 and SK-Hep1 HCC cell lines Overall design: Methods: HepG2 and SK-Hep1 HCC cell lines were acquired from American Type Culture Collection (ATCC) and miR-17 TuD or NC TuD expressing lines were generated. mRNA profiling of miR-17 TuD or NC TuD expressing samples was performed using Illumina NGS. Total RNA was extracted as per manufacturer’s instructions (RNeasy kit, Qiagen). RNA quality was assessed using BioAnalyzer (Agilent). mRNA expression profiles were determined using next-generation sequencing (NGS) on the Illumina HiSeq 2000 platform producing 50bp paired-end reads. Bowtie/TopHat suites were used to align the reads to mouse genome or transcriptome and RSEM were used to quantify gene abundances. Gene level counts were then normalized with the R/Bioconductor package limma using the voom/variance stabilization method.
Publication Title
Lipid Nanoparticle-Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To functionally characterize the role of miR-17 family in HCC, lentiviral vector-based miR inhibitor TuD was used to inhibit miR-17 family of microRNAs in Hep3B cell line
Publication Title
Lipid Nanoparticle-Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 53 Downloadable Samples
- IlluminaHiSeq2000
Description
Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Overall design: Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control
Publication Title
Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma.
Publication Title
TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
We studied the synaptic activity-regulated gene expression response in the human genetic background using cultured human iPSC-derived (hiPSCd) neuronal networks and networks of hiPSCd neurons mixed with mouse primary neurons. Our results confirm that genetic changes affect the synaptic activity-regulated gene program, proposing a functional mechanism how they have driven evolution of human cognitive abilities. Overall design: We compared RNA profiles of untreated hiPSCd neurons and hiPSCd neurons treated with bicuculline and 4-aminopyridine for 1 or 4 hours. Samples were collected from hiPSCd neuron-only cultures and from co-cultures of hiPSCd neurons and mouse primary hippocampal neurons.
Publication Title
Networks of Cultured iPSC-Derived Neurons Reveal the Human Synaptic Activity-Regulated Adaptive Gene Program.
Sample Metadata Fields
Specimen part, Subject
View Samples