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SRP131095
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2500
Description
Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of human cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes tested regulate proliferation, many performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in SCNAs (somatic copy number changes) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue type-specific genetic network architectures underlie SCNA selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive new insights about the genetic network architecture of aneuploidy in tumors. KRTAPs are a class of human genes that promote proliferation in mammary epithelial cells (HMEC), but the mechanism is not understood. We performed RNAseq to study transcriptional changes associated with oeverxepression of KRTAPs and other oncogenes in hTERT-immortalized human mammary epithelial cells. GSEA analysis revealed the top enriched pathways upregulated by KRTAP expression are E2F-mediated regulation of DNA replication, G1-S specific transcription, cell cycle, translation and ribosome. KRTAP-induced mRNA changes are most closely related to those due to CCND1 expression, including induction of E2F1 transcription factor. Overall design: Analysis of whole transcriptome in HMEC overexpressing different human genes.
Publication Title
Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- IlluminaHiSeq2000
Description
c-MYC (MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. Like other classic oncogenes, hyperactivation of MYC leads to collateral stresses onto cancer cells, suggesting that tumors harbor unique vulnerabilities arising from oncogenic activation of MYC. Herein, we discover the spliceosome as a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene, and demonstrate that BUD31 is a splicing factor required for the assembly and catalytic activity of the spliceosome. Core spliceosomal factors (SF3B1, U2AF1, and others) associate with BUD31 and are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total pre-mRNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Importantly, genetic or pharmacologic inhibition of the spliceosome in vivo impairs survival, tumorigenicity, and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers. Overall design: Examination of intron rentention in MYC-ER HMECs, in 4 conditions
Publication Title
The spliceosome is a therapeutic vulnerability in MYC-driven cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression. ECV304 endothelial cells were stimulated with IL-1 100 U/ml in the presence or absence of Aminaphtone 6 g/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray.
Publication Title
Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The goal of this study was to assess whether the presence of HLA-B*35 contributes to activation of ER stress/UPR and inflammation in lcSScPAH PBMC.
Publication Title
The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting, in a context-dependent manner, processes of proliferation, differentiation, and apoptosis1. It has been implicated in human cancer both as an oncogene and a tumor suppressor2. Here we report, for the first time, novel inactivating mutations in the Notch pathway components in over forty percent of the human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the US male population3. Thus far, driver mutations in the FGFR3 and less commonly RAS proteins have been identified4,5. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual specificity phosphatases (DUSPs), thus reducing ERK1/2 phosphorylation. In mouse models, genetic inactivation of Notch signaling leads to ERK1/2 phosphorylation resulting in tumorigenesis in the urinary tract. In recent years, the tumor suppressor role of Notch has been recognized by loss-of-function mutations identified in myeloid cancers6 as well as squamous cell carcinomas of the skin, lung7, and the head and neck8,9. Of the 4 Notch receptors (N1-4), only N1 and 2 have been implicated in human cancer.
Publication Title
A new tumor suppressor role for the Notch pathway in bladder cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression. Overall design: Compared silencing of ATF2SV5 in H3A cells vs. silencing of ATF2WT via Ampliseq whole transcriptome analysis on the Ion Proton
Publication Title
A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Ion Torrent Proton
Description
It is possible to identify the key genes and pathways involved in specific physiological processes using transcriptome analyses. However, these powerful new deep sequencing-based methods have rarely been applied to studies of memory function. We used the bow-tie maze to train rats by exposing them to highly familiar objects or to novel objects. Total RNA sequencing was then used to compare the transcriptome of the perirhinal cortices of naïve control rats and rats exposed to novel and familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats and these included genes coding for transcription factors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures. Overall design: RNA profiles of perirhinal cortex from rats exposed to novel objects (n=5) or familiar objects (n=5) in a recognition memory task were investigated using the Ion Proton System. Controls were naïve rats that had not undergone any behavioural testing (n=4).
Publication Title
Recognition memory-induced gene expression in the perirhinal cortex: A transcriptomic analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 4000
Description
Here we are using RNA-Seq to study the effect of PRR14L knockdown on transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage. Overall design: RNAseq was performed on individual CFU-GM with shRNA-mediated PRR14L knockdown and scramble control to study the effects of PRR14L knockdown on the transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage.
Publication Title
PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.
Publication Title
Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development
Publication Title
Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples