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GSE40422
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGF signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGF activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
Publication Title
HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGF signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGF activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
Publication Title
HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
GRN163L is a potent and specifictelomeraseinhibitor and in clinical trials for cancer treatment. To identify the biomarker that might predict response to telomease based therapy, gene expression analysis of the cancer cell lines after treatiment with telomerase inhibitor Imetelstat (GRN163L) was performed.
Publication Title
Interleukin 8 is a biomarker of telomerase inhibition in cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Effect of SHMT1 knockdown on ovarian cancer tumor growth was analyzed
Publication Title
Serine hydroxymethyl transferase 1 stimulates pro-oncogenic cytokine expression through sialic acid to promote ovarian cancer tumor growth and progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Regulation of the DNA damage response and cell cycle progression is critical for maintaining genome integrity. Here we report that in response to DNA damage, COPS5 deubiquitinates and stabilizes PEA15 in an ATM kinase-dependent manner. PEA15 expression oscillates throughout the cell cycle, and the loss of PEA15 accelerates cell cycle progression by activating CDK6 expression via the c-JUN transcription factor. Cells lacking PEA15 exhibit a DNA damage-induced G2/M checkpoint defect due to increased CDC25C activity and consequentially higher CDK1/Cyclin B activity and accordingly have an increased rate of spontaneous mutagenesis. We find that oncogenic RAS inhibits PEA15 expression and ectopic PEA15 expression blocks RAS-mediated transformation, which can be partially rescued by ectopic expression of CDK6. Finally, we show that PEA15 expression is down regulated in colon, breast and lung cancer samples. Collectively, our results demonstrate that tumor suppressor PEA15 is a regulator of genome integrity and is an integral component of the DNA damage response pathway that regulates cell cycle progression, the DNA-damage-induced G2/M checkpoint and cellular transformation.
Publication Title
PEA15 regulates the DNA damage-induced cell cycle checkpoint and oncogene-directed transformation.
Sample Metadata Fields
Cell line
View Samples- Zea mays
- 22 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: This study is designed to identify genes and processes that are differentially regulated in corn when it is grown with or without weeds through the entire critical weed free period (to V8) or when weeds were removed early in the critical weed free period (at V4) and the plants were allowed to recover until V8. Methods: Corn was grown as described above in field plots near Brookings SD in 2007 and 2008 and RNA was extracted from the top-most leaf tips from four plants per treatment plot. Unidirectional cDNA illumina sequencing libraries were constructed for each sample (pooled leaf tips from the given plot), and were sequenced (some samples were paired end sequenced and some were single end sequenced - all 100 bases for PE and SE reads), quality trimmed, and analyzed using the Tuxedo suite of programs for SE reads of the forward read libraries for each sample. Results: We identified a small number of genes that were differentially expressed in both years. More importantly, gene set enrichment analysis of the data determined that weeds, when present through the critical weed free period impacted phytochrome signaling, defense responses, photosynthetic processes, oxidative stress responses, and various hormone signaling processes. When weeds were removed at V4 and the plants allowed to recover until V8, the weeds still imprinted impacts on phytochrome signaling, oxidative stress, and defense responses. Thus, it appears that weeds presence through the early portion of the critical weed free period, even after removal, induced processes that reduce corn growth and yield that lasted at least through V8. Conclusions: This study represents the first investigation of the impact of the lasting effects of weeds during the early critical weed free period on the transcriptome of corn, and provides additional data on the impact of weeds through the critical weed free period that augments and confirms much of what was observed in similar microarray studies. Overall design: Experimental Design: Samples all collected at the same developmental stage (V8) from three treatments (control, weedy, and weeds removed followed by recovery), in each of two years (2007 and 2008), with two to three biological replicates of each treatment in each year.
Publication Title
Weed presence altered biotic stress and light signaling in maize even when weeds were removed early in the critical weed-free period.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma.
Publication Title
miR-146a promotes the initiation and progression of melanoma by activating Notch signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina Genome Analyzer
Description
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. Overall design: WI-38 cells were either infected with BRAFV600E or Empty retroviral vectors and small RNA were prepared from these cells. As an additional control, WI-38 cells were serum starved and used to generate quiscent cells, which were also used to prepase small RNA. The small RNA were then used to generate small RNA library and were used on Illumina genome analyzer.
Publication Title
miR-146a promotes the initiation and progression of melanoma by activating Notch signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Malignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Overall design: Transcriptomic analysis of two different stages of gliomagenesis
Publication Title
Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples