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accession-icon SRP098927
A Cross-Species Approach Identifies MELK as a Potential Therapeutic Target in Prostate Cancer
  • organism-icon Mus musculus
  • sample-icon 912 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Genetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples

Publication Title

Identification of potential therapeutic targets in prostate cancer through a cross-species approach.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE36526
Hes6 drives a network with therapeutic potential in castrate-resistant prostate cancer
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip

Description

Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance in early prostate cancer, other factors such as c-Myc and the E2F family also play a role in later stage disease. Hes6 is a transcription co-factor that has been associated with neurogenesis during gastrulation, a neuroendocrine phenotype in the prostate and metastasis in breast cancer but its role in prostate cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and AR and drives castration resistance in prostate cancer. Hes6 activates a cell-cycle enhancing transcriptional network that maintains tumour growth and nuclear AR localization in castrate conditions. We show aphysical interaction between E2F1 and both Hes6 and AR, and suggest a co-dependency of these transcription factors in castration-resistance. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted. We have therefore shown for the first time the critical role of Hes6 in the development of CRPC and identified its potential in patient specific therapeutic strategies.

Publication Title

HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.

Sample Metadata Fields

Specimen part, Disease, Cell line

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accession-icon GSE36434
Hes6 expression is controlled by c-Myc and the AR to promote E2F1 activity and poor outcome in castrate-resistant prostate cancer (LNCaP)
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V3.0 expression beadchip

Description

Hes6 is a transcription co-factor that is associated with stem cell characteristics in neural tissue, but its role in cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and the AR and can drive castration resistance in xenografts of the androgen-dependent LNCaP prostate cancer cell line model. Hes6 activates a cell cycle enhancing transcriptional network that maintains tumour growth in the absence of circulating androgen but with maintained nuclear AR. We demonstrate interaction between E2F1, the AR and Hes6 and show the co-dependency of these factors in the castration-resistant setting. In the clinical setting, we have discovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which could be pharmacologically targeted.

Publication Title

HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.

Sample Metadata Fields

Cell line

View Samples
accession-icon GSE47875
SEQC Toxicogenomics Study: microarray data set
  • organism-icon Rattus norvegicus
  • sample-icon 105 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

The comparative advantages of RNA-Seq and microarrays in transcriptome profiling were evaluated in the context of a comprehensive study design. Gene expression data from Illumina RNA-Seq and Affymetrix microarrays were obtained from livers of rats exposed to 27 agents that comprised of seven modes of action (MOAs); they were split into training and test sets and verified with real time PCR.

Publication Title

The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE9686
Human colon expression in healthy, CD, treated CD, and UC
  • organism-icon Homo sapiens
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Activation of inflammatory pathways in human IBD

Publication Title

Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE54169
Differential regulation patterns of anti-CD20 mAbs in MCL
  • organism-icon Homo sapiens
  • sample-icon 74 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

We investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation.

Publication Title

Differential regulation patterns of the anti-CD20 antibodies obinutuzumab and rituximab in mantle cell lymphoma.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE44097
-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/-catenin signaling
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with -catenin siRNA and identified -catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published -catenin target genes found in the PubMed and the GEO databases.

Publication Title

Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE26647
Gene Expression Changes Associated with the Progression of Intraductal Papillary Mucinous Neoplasms
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN.

Publication Title

Gene expression changes associated with the progression of intraductal papillary mucinous neoplasms.

Sample Metadata Fields

Disease, Disease stage, Subject

View Samples
accession-icon GSE15946
Determining lovastatin-induced differences in expression between statin sensitive and insensitive MM cells
  • organism-icon Homo sapiens
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The goals of this study were to determine global differences in transcript expression and regulation between MM cells that are sensitive or insensitive to lovastatin-induced apoptosis. To this end, two sensitive (KMS11 and H929) and two insensitive (LP1 and SKMM1) MM cell lines treated with 20uM lovastatin or an ethanol vehicle control for 16 hours. mRNA was extracted and prepared for mRNA expression microarrays (HG-U133 Plus 2) in triplicate.

Publication Title

Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma.

Sample Metadata Fields

Specimen part, Cell line, Treatment

View Samples
accession-icon GSE84809
Microarray analysis of white adipose tissue and liver from CD301b+ MNP-depleted mice
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Tissue-resident mononuclear phagocytes (MNPs) in metabolic organs contribute to the regulation of whole body metabolism. CD301b+ MNPs are a subset of MNPs that are found in most peripheral organs including metabolic organs. In a mouse model in which CD301b+ MNPs can be selectively and transiently depleted, we examined the impact of the depletion on gene expression in the white adipose tissue and the liver.

Publication Title

CD301b(+) Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha.

Sample Metadata Fields

Specimen part

View Samples
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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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