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Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Targeted interference of sin3a-tgif1 function by SID decoy treatment inhibits WNT signaling and invasion in triple negative breast cancer cells. MDA-MB-231 cells were treated with scrambled SID control, 2.5M SID peptide or untreated for 24h.
Publication Title
Targeted interference of SIN3A-TGIF1 function by SID decoy treatment inhibits Wnt signaling and invasion in triple negative breast cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Triple negative breast cancer (TNBC) is characterized by a poorly differentiated phenotype and limited treatment options. Aberrant epigenetics in this subtype represent a potential therapeutic opportunity, but a better understanding of the mechanisms contributing to the TNBC pathogenesis is required. The SIN3 molecular scaffold performs a critical role in multiple cellular processes, including epigenetic regulation, and has been identified as a potential therapeutic target. Using a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID), we investigated the functional consequences of selectively blocking the paired amphipathic helix (PAH2) domain of SIN3. Here, we report the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the TNBC stem cell phenotype and epithelial to mesenchymal transition (EMT). Tat-SID peptide blocked the interaction between SIN3A and PF1, leading to epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers. Importantly, Tat-SID treatment led to a reduction in primary tumor growth and disseminated metastatic disease in vivo. In support of these findings, knockdown of PF1 expression phenocopied treatment with Tat-SID both in vitro and in vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting.
Publication Title
Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Triple negative breast cancers (TNBC) lacking estrogen, progesterone and HER2 receptors account for 10-20% of breast cancer and are indicative of poor prognosis. The development of effective treatment strategies therefore represents a pressing unmet clinical need. We previously identified a molecularly-targeted approach to target aberrant epigenetics of TNBC using a peptide corresponding to the SIN3 interaction domain (SID) of MAD. SID peptide selectively blocked binding of SID-containing proteins to the paired -helix (PAH2) domain of SIN3, resulting in epigenetic and transcriptional modulation of genes associated with epithelial-mesenchymal transition (EMT). To find small molecule inhibitor (SMI) mimetics of SID peptide we performed an in silico screen for PAH2 domain-binding compounds. This led to the identification of the avermectin macrocyclic lactone derivatives selamectin and ivermectin (Mectizan) as candidate compounds. Both selamectin and ivermectin phenocopied the effects of SID peptide to block SIN3-PAH2 interaction with MAD, induce expression of CDH1 and ESR1 and restore tamoxifen sensitivity in MDA-MB-231 human and MMTV-Myc mouse TNBC cells in vitro. Treatment with selamectin or ivermectin led to transcriptional modulation of genes associated with EMT and maintenance of a cancer stem cell phenotype in TNBC cells. This resulted in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo. Underlining the potential of avermectins in TNBC, pathway analysis revealed that selamectin also modulated the expression of therapeutically-targetable genes. Consistent with this, an unbiased drug screen in TNBC cells identified selamectin-induced sensitization to a number of drugs, including those targeting modulated genes.
Publication Title
Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.
Sample Metadata Fields
Specimen part, Cell line
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- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Inrauterine growth restriction was induced by chronic hyper insulinemia in pregnant rats and differential gene expression was studied using affymetrix rat genome RAE230A.Data was analysed using SAM.
Publication Title
Adult hypertension in intrauterine growth-restricted offspring of hyperinsulinemic rats: evidence of subtle renal damage.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE5799- Staphylococcus aureus
- 12 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes.
Publication Title
A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A permantly active form of the oncogene Akt was expressed in the keratinocytes of the basal proliferative layer of the epidermis. Stem cells of the hair follicle expressing the cell surface marker CD34 were isolated. RNA form the CD34(+) and CD34(-) keratinocytes was extracted and and hybridized to Mouse Genome 430 2.0 Affymetrix arrays.
Publication Title
Akt signaling leads to stem cell activation and promotes tumor development in epidermis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The etiology of trauma-hemorrhage shock-induced acute lung injury has been difficult to elucidate due, at least in part, to the inability of in vivo studies to separate the non-injurious pulmonary effects of trauma-hemorrhage from the tissue injurious ones. To circumvent this in vivo limitation, we utilized a model of trauma-hemorrhagic shock (T/HS) in which T/HS-lung injury was abrogated by dividing the mesenteric lymph duct. In this way, it was possible to separate the pulmonary injurious response from the non-injurious systemic response to T/HS by comparing the pulmonary molecular response of rats subjected to T/HS which did and did not develop lung injury as well as to non-shocked rats. Utilizing high-density oligonucleotide arrays and treatment group comparisons of whole lung tissue collected at 3 hours after the end of the shock or sham-shock period, 139 of the 8,799 assessed genes were differentially expressed.
Publication Title
Molecular signatures of trauma-hemorrhagic shock-induced lung injury: hemorrhage- and injury-associated genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
We analysed the transcriptional signature in endothelial cells extracted from the bone marrow of mice engrafted with human AML and compared it to the one of mice engrafted with human normal hematopoietic cells Overall design: Immunodeficient mice were transplanted with human AML cells derived from patients, or with normal human hematopoietic cells derived from cord blood. Mice were sacrificed once assessed the bone marrow engraftment, and the bones were processed to isolate endothelial cells using the CD31 marker. RNA was extracted, sequencing libraries were prepared and sequenced.
Publication Title
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples