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SRP036839
Drosophila melanogaster
48 Downloadable Samples
Illumina HiSeq 2000
Description
Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, we analyzed the mechanism underlying glucose repression of digestive enzymes in the adult Drosophila midgut. We demonstrate that glucose represses the expression of many carbohydrases and lipases. Our data reveal that the consumption of nutritious sugars stimulates the secretion of the transforming growth factor ß (TGF-ß) ligand, Dawdle, from the fat body. Dawdle then acts via circulation to activate TGF-ß/Activin signaling in the midgut, culminating in the repression of digestive enzymes that are highly expressed during starvation. Thus, our study not only identifies a mechanism that couples sugar sensing with digestive enzyme expression but points to an important role of TGF-ß/Activin signaling in sugar metabolism. Overall design: RNA-sequencing of whole guts from Drosophila melannogaster OregonR adult females was performed under three feeding conditions: Standard medium, glucose, and agar. Three biological repeats were performed for each condition.
Publication Title
Transforming growth factor β/activin signaling functions as a sugar-sensing feedback loop to regulate digestive enzyme expression.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina humanRef-8 v2.0 expression beadchip
Description
To investigate the mechanism of telomerase regulation in BCR-ABL positive cells due to its clinical value, we studied the catalytic component of telomerase, TERT. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at the mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells. TRAP assay also revealed that Gleevec treatment significantly reduced TA specifically in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Although Gleevec down-regulated hTERT mRNA level, the protein level of hTERT remained unchanged. Therefore, Gleevec-induced-TA decrease is not due to the alteration in telomerase subunits expression. It could be presumably due to posttranslational modification of hTERT, possibly through multiple signaling pathways. We have found that Gleevec reduced the tyrosine phosphorylation of hTERT by BCR-ABL, which is associated with the nucleoplasm localization of hTERT from nucleoli sequesters. These findings reveal unknown functions and regulations of telomerase by BCR-ABL.
Publication Title
Regulation of hTERT by BCR-ABL at multiple levels in K562 cells.
Sample Metadata Fields
Sex, Disease, Cell line
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Molecular pathways activated in MALT lymphoma are not well defined.
Publication Title
Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A transcriptional repressor co-regulatory network governing androgen response in prostate cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM.
Publication Title
Determinants of sensitivity to DZNep induced apoptosis in multiple myeloma cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
Deregulation of the Androgen Receptor (AR) transcriptional network is a common hallmark in prostate cancers. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of cofactors. In prostate cancers, AR transcription collaborators are frequently aberrantly over-expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, the prostate cancer recurrent fusion gene, ERG, was shown to promote tumor progression by acting as a repressor of AR signaling. However, the exact mechanics and the functional consequences associated with this crosstalk between ERG and AR still remains relatively unknown. Interestingly, through chromatin immunoprecipitation coupled with massively parallel sequencing, we discover that ERG and other commonly over-expressed transcriptional co-repressors (HDAC1, HDAC2, HDAC3 and EZH2) are wired into an AR-centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. We show that ERG represses several AR target genes involved in epithelial differentiation. Furthermore, we demonstrated that suppression of the androgen-induced gene, Vinculin, by ERG and histone deacetylases increases cancer cell invasiveness. From our results, we propose that ERG, histone deactelyases and the histone methyltransferase, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, in part through modulating the transcriptional output of AR.
Publication Title
A transcriptional repressor co-regulatory network governing androgen response in prostate cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We demonstrated that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, induce robust apoptosis in AML cells through increased ROS production and ER stress.
Publication Title
The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Deregulation of the Androgen Receptor (AR) transcriptional network is a common hallmark in prostate cancers. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of cofactors. In prostate cancers, AR transcription collaborators are frequently aberrantly over-expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, the prostate cancer recurrent fusion gene, ERG, was shown to promote tumor progression by acting as a repressor of AR signaling. However, the exact mechanics and the functional consequences associated with this crosstalk between ERG and AR still remains relatively unknown. Interestingly, through chromatin immunoprecipitation coupled with massively parallel sequencing, we discover that ERG and other commonly over-expressed transcriptional co-repressors (HDAC1, HDAC2, HDAC3 and EZH2) are wired into an AR centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. We show that ERG represses several AR target genes involved in epithelial differentiation. Furthermore, we demonstrated that suppression of the androgen induced gene, Vinculin, by ERG and histone deacetylases increases cancer cell invasiveness. From our results, we propose that ERG, histone deactelyases and the histone methyltransferase, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, in part through modulating the transcriptional output of AR.
Publication Title
A transcriptional repressor co-regulatory network governing androgen response in prostate cancers.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 47 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Gene expression profiling of extranodal nasal-type NK/T cell lymphoma and other EBV-associated lymphoid proliferation disease patients was analyzed to elucidate association between JAK-STAT pathway and canonical or non-canonical PRC2/EZH2 target pathways using Illumina HumanRef-8 v3 chips.
Publication Title
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Sample Metadata Fields
Disease
View Samples