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accession-icon GSE3425
Silencing of microRNAs in vivo with "antagomirs"
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Using a novel class of chemically-engineered oligonucleotides, termed "antagomirs", we studied the biological significance of silencing miR-122 in the liver of mice at the mRNA level

Publication Title

Silencing of microRNAs in vivo with 'antagomirs'.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP069243
Genome-wide expression profile in FH-deficient (UOK262) vs FH-competent (UOK262pFH) human cells derived from metastatsis to the mediastinum of a HLRCC patient
  • organism-icon Homo sapiens
  • sample-icon 270 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500

Description

Comparison of the transcriptome of human kideny cancer cells either wild-type for FH or FH-deficient. The UOK262 cells were isolated from mediastinum metastasis of a HLRCC patient (Yang et al. Cancer Genetics and Cytogenetics, Volume 196, Issue 1, 1 January 2010, Pages 45–55). FH function was restored in the UOK262 by re-expressing the FH transcript from an exogenous plasmid. Overall design: Examination of gene transciption in 2 cell types.

Publication Title

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP069245
Genome-wide expression profile in Fh1-competent vs Fh1-deficient mouse kidney cells
  • organism-icon Mus musculus
  • sample-icon 200 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Comparison of the transcriptome of immortalised mouse kidney epithelial cells either wt for Fh1 or Fh1-deficient. The cells were isolated from kidneys of P5 mouse(see Frezza et al, Nature 2011). Briefly, Fh1_fl (flox) are wt for Fh1 (floxed cassette not excised), clone 1 and clone 19 are two different Fh1-deificent clones (floxed cassette excised) and Rec are clone 19 with reconstituted Fh1 expression from exogenous plasmid. Overall design: Examination of gene transciption in 4 cell types.

Publication Title

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE37645
The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective -secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC.

Publication Title

The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models.

Sample Metadata Fields

Specimen part

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accession-icon GSE9599
Coordinated over-expression of genes in the EGFR pathway predicts sensitivity to EGFR inhibition in pancreatic cancer
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Tumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis

Publication Title

Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP064316
Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. Overall design: Sequencing of blood RNA from five healthy individuals (biological replicates) plus technical replicate of one sample and detection of circRNAs.

Publication Title

Identification and Characterization of Circular RNAs As a New Class of Putative Biomarkers in Human Blood.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP007641
small RNA profiling in human cell line following Dicer silencing
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

microRNAs (miRNAs) are a large class of small non-coding RNAs which post-transcriptionally regulate the expression of a large fraction of all animal genes and are important in a wide range of biological processes. Recent advances in high-throughput sequencing allow miRNA detection at unprecedented sensitivity, but the computational task of accurately identifying the miRNAs in the background of sequenced RNAs remains challenging. For this purpose we have designed miRDeep2, a substantially improved algorithm which identifies canonical and non-canonical miRNAs such as those derived from transposable elements and informs on high-confidence candidates that are detected in multiple independent samples. Analyzing data from seven animal species representing the major animal clades, miRDeep2 identified miRNAs with an accuracy of 98.6-99.9% and reported hundreds of novel miRNAs. To test the accuracy of miRDeep2, we knocked down the miRNA biogenesis pathway in a human cell line and sequenced small RNAs before and after. The vast majority of the >100 novel miRNAs expressed in this cell line were indeed specifically down-regulated, validating most miRDeep2 predictions. Last, a new miRNA expression profiling routine, low time and memory usage and user-friendly interactive graphic output can make miRDeep2 useful to a wide range of researchers." Overall design: high-throughput sequencing was used to profile small RNA expression in a human MCF-7 cell line before and after Dicer knock-down

Publication Title

miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades.

Sample Metadata Fields

Cell line, Subject

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accession-icon SRP038919
Transcriptome wide identification of Dicer binding in human and C. elegans reveals a variety of substrates (HEK PAR-CLIP)
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Dicer is a deeply conserved endoribonuclease with key functions in small RNA biogenesis. Here we employed PAR-CLIP/iPAR-CLIP to identify direct Dicer binding sites in the transcriptomes of human cells and human. We found hundreds of novel miRNAs and non-canonical Dicer substrates with high sensitivity. Small RNA production depended on structure of the binding site and is globally biased towards the 5'' arm of hairpins. Unexpectedly, in both species Dicer bound numerous hairpins inside mRNAs without observable small RNA production. Our data revealed ~100 mRNAs of protein coding genes to be targeted in both human and worm. These mRNAs significantly overlapped with the RNAi pathway. We also, unexpectedly, found that mitochondrial transcripts are Dicer targets in both species. We demonstrate functional consequences of Dicer binding by perturbation analysis. Taken together,we provide the first genome-wide catalog of direct Dicer targets. Our results suggest widespread function outside of miRNA biogenesis. Overall design: PAR-CLIP basically as described previously (Hafner et al. 2010).

Publication Title

A variety of dicer substrates in human and C. elegans.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP050055
A variety of Dicer substrates in human and C. elegans (HEK RNA-seq)
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

The endoribonuclease Dicer is known for its central role in the biogenesis of eukaryotic small RNAs/microRNAs. Despite its importance, Dicer target transcripts have not been directly mapped. Here, we apply biochemical methods to human cells and C. elegans and identify thousands of Dicer binding sites. We find known and hundreds of novel miRNAs with high sensitivity and specificity. We also report structural RNAs, promoter RNAs, and mitochondrial transcripts as Dicer targets. Interestingly, most Dicer binding sites reside on mRNAs/lncRNAs and are not significantly processed into small RNAs. These passive sites typically harbor small, Dicer-bound hairpins within intact transcripts and generally stabilize target expression. We show that passive sites can sequester Dicer and reduce microRNA expression. mRNAs with passive sites were in human and worm significantly associated with processing-body/granule function. Together, we provide the first transcriptome-wide map of Dicer targets and suggest conserved binding modes and functions outside the miRNA pathway. Overall design: Regulatory impact of Dicer binding was assessed by knock down experiments in human HEK293 cells. Drosha knockdown and mock transfections were used as controls. Knockdown was performed with two independent siRNAs each. In total 5 samples.

Publication Title

A variety of dicer substrates in human and C. elegans.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP038921
Transcriptome wide identification of Dicer binding in human and C. elegans reveals a variety of substrates (HEK RNA-Seq)
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Dicer is a deeply conserved endoribonuclease with key functions in small RNA biogenesis. Here we employed PAR-CLIP/iPAR-CLIP to identify direct Dicer binding sites in the transcriptomes of human cells and human. We found hundreds of novel miRNAs and non-canonical Dicer substrates with high sensitivity. Small RNA production depended on structure of the binding site and is globally biased towards the 5'' arm of hairpins. Unexpectedly, in both species Dicer bound numerous hairpins inside mRNAs without observable small RNA production. Our data revealed ~100 mRNAs of protein coding genes to be targeted in both human and worm. These mRNAs significantly overlapped with the RNAi pathway. We also, unexpectedly, found that mitochondrial transcripts are Dicer targets in both species. We demonstrate functional consequences of Dicer binding by perturbation analysis. Taken together,we provide the first genome-wide catalog of direct Dicer targets. Our results suggest widespread function outside of miRNA biogenesis. Overall design: Regulatory impact of Dicer binding was assessed by knock down experiments in human HEK293 cells. Drosha knockdown and mock transfections were used as controls. In total 3 samples.

Publication Title

A variety of dicer substrates in human and C. elegans.

Sample Metadata Fields

No sample metadata fields

View Samples
...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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