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GSE89766
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Autophagy plays important roles in malignant pathogenesis and drug resistance. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC). ROC-325 exhibited superior in vitro anticancer effects than the existing autophagy inhibitor hydroxychloroquine in 12 different tumor models with diverse genetic backgrounds. Focused studies of the mechanism of action and efficacy of ROC-325 in RCC cells showed that drug treatment induced hallmark characteristics of autophagy inhibition including accumulation of autophagosomes with undegraded cargo, lysosomal deacidification, p62 stabilization, and disruption of autophagic flux. Subsequent experiments showed that ROC-325 antagonized RCC growth and survival in an ATG5/7-dependent manner, induced apoptosis, and exhibited favorable selectivity. Oral administration of ROC-325 to mice bearing 786-0 RCC xenografts was well tolerated, significantly more effective at inhibiting tumor progression than HCQ, and inhibited autophagy in vivo.
Publication Title
Disruption of Autophagic Degradation with ROC-325 Antagonizes Renal Cell Carcinoma Pathogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We identified LAMP3 as a key driver gene of anti-viral subnetwork genes in cervical cancer patients. Therefore we tested this prediction using an in vitro system. This is the first direct demonstration of LAMP3 regulatory role in interferon-dependent immune response.
Publication Title
Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer.
Sample Metadata Fields
Disease, Cell line, Treatment, Time
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Expression profiles of wild type migratory border cells (WTBC), non-migrating slbo mutant border cells (slboBC) and non-migrating follicle cells (FC)
Publication Title
Systematic analysis of the transcriptional switch inducing migration of border cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Seed dormancy is the inability for seeds to germinate even under favorable conditions. In the Arabidopsis Landsberg <i>erecta</i> (L<i>er</i>) ecotype, 2 weeks of dry storage, called after-ripening, is sufficient to relieve seed dormancy. Such seed is referred to as after-ripened (AR) and has a high rate of germination when imbibed. While widespread transcriptome changes have been previously observed with seed dormancy loss, this experiment was designed to characterize transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive <i>sleepy1-2</i> (<i>sly1-2</i>) mutant. The <i>SLY1</i> gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. In the <i>sly1-2</i> mutant, GA-directed DELLA proteolysis cannot occur leading to DELLA protein accumulation and increased dormancy. <i>sly1-2</i> mutant seeds are fully dormant at 2 weeks of dry storage (0% germination), but germinate well with very long after-ripening (51% germination after 19 months). <i>sly1-2</i> seed germination can also be rescued by overexpression of the GA receptor, <i>GA-INSENSITIVE DWARF1b</i> (<i>GID1b-OE</i>), which resulted in 74% germination at 2 weeks of dry storage. In this experiment, we compared seeds of wild-type L<i>er</i> at 2 weeks of dry storage (non-dormant), dormant <i>sly1-2</i> (2 weeks of dry storage; <i>sly1-2</i>(D)), long after-ripened <i>sly1-2</i> (non-dormant, 19 months of dry storage; <i>sly1-2</i>(AR)), and <i>sly1-2 GID1b-OE</i> (non-dormant, 2 weeks of dry storage). Samples were collected at two imbibition timepoints: 1) a 0h timepoint after 4 days at 4°C, and 2) a 12h timepoint after 4 days at 4°C followed by 12 hours in the light at 22°C. These timepoints were selected to capture the transcriptomes at an early and late time in Phase II of imbibition. Using this experimental design we were able to determine transcriptome differences associated with seed dormancy in the <i>sly1-2</i> mutation (L<i>er</i> wt vs <i>sly1-2</i>(D)), and changes associated with <i>sly1-2</i> dormancy loss through dry after-ripening (<i>sly1-2</i>(AR) vs <i>sly1-2</i>(D)) or through <i>GID1b</i>-overexpression (<i>sly1-2 GID1b-OE</i> vs <i>sly1-2</i>(D)). Seeds for L<i>er</i> wt, <i>sly1-2</i>(D), and <i>sly1-2 GID1b-OE</i> were grown alongside each other under the same conditions and after-ripened for 2 weeks. Seeds from <i>sly1-2</i>(AR) were grown under the same conditions in advance of the other lines to allow for the long after-ripening requirement. RNA was extracted using a phenol-chloroform-based extraction from three biological replicates per treatment.
Publication Title
Transcriptional mechanisms associated with seed dormancy and dormancy loss in the gibberellin-insensitive sly1-2 mutant of Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Time
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plant embryos can survive years in a desiccated, quiescent state within seeds. In many species, seeds are dormant and unable to germinate at maturity. They acquire the capacity to germinate through a period of dry storage called after-ripening (AR), a biological process that occurs at 5-15% moisture when most metabolic processes cease. Because stored transcripts will be among the first proteins translated upon water uptake, they likely impact germination potential. Transcriptome changes associated with the increased seed dormancy of the GA-insensitive <i>sly1-2</i> mutant, and with dormancy loss through <i>sly1-2</i> after-ripening or constitutive overexpression of the GA receptor (GID1b) were characterized in dry seeds. This experiment used the same seed batches as a previous experiment (E-MTAB-4782) to characterize transcriptional changes associated with the increased seed dormancy and dormancy loss in imbibing seeds. The <i>SLY1</i> gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. In the <i>sly1-2</i> mutant, GA-directed DELLA proteolysis cannot occur leading to DELLA protein accumulation and increased dormancy. <i>sly1-2</i> mutant seeds are fully dormant at 2 weeks of dry storage (0% germination), but germinate well with very long after-ripening (51% germination after 19 months). <i>sly1-2</i> seed germination can also be rescued by overexpression of the GA receptor, <i>GA-INSENSITIVE DWARF1b</i> (<i>GID1b-OE</i>), which resulted in 74% germination at 2 weeks of dry storage. In this experiment, we sampled dry seeds of wild-type L<i>er</i> at 2 weeks of dry storage (non-dormant), dormant <i>sly1-2</i> (2 weeks of dry storage; <i>sly1-2</i>(D)), long after-ripened <i>sly1-2</i> (non-dormant, 19 months of dry storage; <i>sly1-2</i>(AR)), and <i>sly1-2 GID1b-OE</i> (non-dormant, 2 weeks of dry storage). This experimental design allowed comparison between these transcriptomes in dry seeds to determine if dry seed stored mRNA differences contribute to the dormancy phenotypes observed once seeds are imbibed. Seeds for L<i>er</i> wt, <i>sly1-2</i>(D), and <i>sly1-2 GID1b-OE</i> were grown alongside each other under the same conditions and after-ripened for 2 weeks. Seeds from <i>sly1-2</i>(AR) were grown under the same conditions in advance of the other lines to allow for the long after-ripening requirement. RNA was extracted using a phenol-chloroform-based extraction from three biological replicates per treatment.
Publication Title
Biology in the Dry Seed: Transcriptome Changes Associated with Dry Seed Dormancy and Dormancy Loss in the Arabidopsis GA-Insensitive sleepy1-2 Mutant
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Genome wide gene expression profile of the lrx1 root hair mutant and the suppressor mutations lrx1 rol1-1 and lrx1 rol1-2.
Publication Title
The Arabidopsis root hair cell wall formation mutant lrx1 is suppressed by mutations in the RHM1 gene encoding a UDP-L-rhamnose synthase.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 27 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Drosophila imaginal disc growth factors (IDGFs) comprise a small protein family of six members belonging to chitinase-like proteins (CLPs), which bind to, but do not cleave chitin or similar carbohydrates. IDGF2 is the prototypical member with known structure and reported to induce the proliferation of imaginal disc cells Cl.8+ in vitro. We characterized the effects of recombinant IDGF2 on tissue culture cells in vitro. We show that it is involved in cell protection from serum deprivation, as well as from the toxic effects of some xenobiotics and metabolites, when the cells are cultivated in serum-free medium conditions. Our results revealed that IDGF2 does not activate insulin pathway. Microarray-based gene expression analysis identified several IDGF2-dependent genes, including genes implicated in innate immune response, Wnt signaling and genes involved in the response to xenobiotics. Consistently, we observed that IDGF2 can be induced in vivo by aseptic or septic injury and high concentration of IDGF2 was detected in garland and pericardial nephrocytes. Our results suggest that IDGF2 is an important and abundant component of Drosophila hemolymph, which shows cytoprotective effects on insect cells in vitro and works as a modulator of multiple signaling pathways involved in morphogenesis, homeostasis and activation of innate immune response.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line, Compound
View Samples