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SRP064742
Drosophila melanogaster
8 Downloadable Samples
Illumina HiSeq 2000
Description
The importance of the role of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore co-expressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of mir-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in highly penetrant pleiotropic developmental defects. We further show that this novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and likely reflects the more general cis-regulation of expression of individual miRNAs. Thus, our results reveal a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift biological response. Overall design: RNA was extracted from Drosophila third instar larval eye discs of animals grown in standard conditions; Illumina HiSeq2000 Next Gen RNA Sequencing was performed, and differential expression of genes was assessed in wild-type vs unchecked miR-998 expression
Publication Title
Novel regulation and functional interaction of polycistronic miRNAs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Expression of dE2F1 induces proliferation and apoptosis. We sought to perform an unbiased analysis of the effect of co-expression of miR-11
Publication Title
mir-11 limits the proapoptotic function of its host gene, dE2f1.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Third instar larval eye discs provide an in vivo model for cell cycle exit studies. Posterior to the Second Mitotic Wave proliferation is absent in a wild type eye disc. Inactivating mutations in tumor suppressor-like genes can lead to genome wide changes in gene expression that allow for inappropriate bypass of cell cycle exit signals posterior to the Second Mitotic Wave.
Publication Title
Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to identify genes that are differentially expressed in the absence of miR-998 expression.
Publication Title
An intronic microRNA links Rb/E2F and EGFR signaling.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 14 Downloadable Samples
- NextSeq 500
Description
We characterized the Drosophila third instar eye disc using single cell RNA-seq and labelled the multiple cell populations. The results identified a novel transcriptional switch in photoreceptors relating to axonal projections. We then performed single cell RNA-seq on rbf (Rb) mutants and compared the results to the WT cell populations. This identified a specific cell population only in the Rb mutant tissue. This cell population has an upregulation of HIF1A and glycolitic genes such as Aldolase and Lactate dehydrogenase. As a result these cells produce lactate and undergo apoptosis. We also show this process to be directly regulated by E2F/Dp. The paper uncovers a novel metabolic aspect of Rb/E2F dependent apoptosis. Overall design: examining WT and Rb mutants third instar eye disc using single cell RNA-seq
Publication Title
Single cell RNA-sequencing identifies a metabolic aspect of apoptosis in Rbf mutant.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Apoptosis is an important process to eliminate cells from tissue which have incurred irreparable DNA damage. While dE2F1/dDP complexes respond to such damage by transcriptionally activating apoptotic genes, previous data suggests that activation of the previously characterized apoptotic target genes of dE2F1/dDP alone may not be the only gene regulation important for gamma irradiation-induced apoptosis. Here we report that following irradiation in dDP mutant 3rd instar larval eye imaginal discs, many genes important for oxidative phosphorylation are down-regulated, which are not down-regulated following irradiation in wild type eye discs.
Publication Title
Loss of dE2F compromises mitochondrial function.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Proliferation of prostate cancer cells, LNCaP, is suppressed by casodex. This suppression requires expression of AR coregulator, NCOR1.
Publication Title
Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
AR transcriptional activity is regulated by DHT
Publication Title
Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
COUP-TFII, a member of the nuclear receptor superfamily plays a critical role in angiogenesis and organogenesis during embryonic development. Our results indicate that COUP-TFII expression is profoundly upregulated in prostate cancer patients and might serves as biomarker for recurrence prediction. Thus we conduct transcriptome comparison of control and COUP-TFII depleted PC3 cells to gain genomic insights on the biological processes that COUP-TFII is involved in prostate cancer cells. Ingenuity Pathway Analysis (IPA) shows that the most prominent altered pathways in the COUP-TFII depleted cells are related to cell growth; cell cycle progression and DNA damage response. Indeed many growth related genes including E2F1, p21, CDC25A, Cyclin A and Cyclin B are changed in COUP-TFII knockdown cells, suggesting that COUP-TFII might be an important regulator for prostate cancer cell growth. Further functional assays from cells and mice genetic studies confirm the hypothesis that COUP-TFII serve as the major regulator to control prostrate cancer growth. Together, results provide insight into the role of COUP-TFII in prostate tumorigenesis.
Publication Title
COUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- (ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)
Description
The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a first-in-field approach to target AR expression and function and improve outcomes in CRPC.
Publication Title
GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex.
Sample Metadata Fields
Cell line
View Samples