To investigate the specific gene expression program by which mutant-p53 and Pin1 control invasion and metastasis in breast cancer cells, we compared the transcriptomic profile of control, mutant-p53 depleted or Pin1 depleted MDA-MB-231 cells.
A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.
Cell line
View SamplesWe used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing .
Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma.
No sample metadata fields
View SamplesGrowth of the drosophila eye imaginal discs is controlled by the activation of Notch in the dorsal-ventral boundary. Overexpression in the eye disc of the Notch ligand Delta together with lola and pipsqueak from the GS(2)88A8 line induces tumoral growth. We used microarray to analyze the expression profile of tumoral discs.
Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.
No sample metadata fields
View SamplesRecent data demonstrate that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways. This network model suggests why inhibition of a single component of a canonical pathway, even when targeting a mutationally activated driver of cancer, has insufficiently dramatic effects on the treatment of cancer. The biological outcome of signals propagated through a network is inherently more robust and resistant to inhibition of a single network component due to compensatory and redundant signaling events. In this study, we performed a functional chemical genetic screen analogous to synthetic lethal screening in yeast genetics to identify novel interactions between signaling inhibitors that would not be predicted based on our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. Among the most robust and surprising results was synergy between sorafenib, a multi-kinase inhibitor with activity against Raf, and diclofenac, a non-steroidal anti-inflammatory drug (NSAID). This synergy did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. The NSAIDs celecoxib and ibuprofen could qualitatively substitute for diclofenac. Similarly, the MEK inhibitor PD325901 and the Raf inhibitor RAF265 could qualitatively substitute for sorafenib. These drug substitution experiments suggest that inhibition of cyclo-oxygenase and MAP kinase signaling are components of the observed synergistic cytotoxicity. Genome-wide expression profiling demonstrates synergy-specific down-regulation of survival-related genes. This study provides proof of principle that synthetic lethal screening can uncover novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially depending on unexplored components of the cell genotype.
Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.
Cell line, Treatment
View SamplesUnderstanding the underlying mechanisms of the well-established platelet hyporeactivity in neonates, would be of great relevance for both improving the clinical management of neonates, a population with a higher bleeding risk than adults (especially among sick and preterm infants), and getting new insights onto the regulatory mechanisms of platelet biology. Transcriptome analysis is a useful tool to identify mRNA signature affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never been reported. Here, we used, for the first time, mRNA expression array to compare the platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories.
Comprehensive comparison of neonate and adult human platelet transcriptomes.
Specimen part
View SamplesHeLa cells transfected to express KDELR1 and HeLa cells incubated with KDEL-Bodipy peptide
Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi.
Cell line, Treatment
View SamplesThis study is part of previous epidemiologic project, including a population-based survey (Sao Paulo Ageing & Health study (SPAH Study). The data from this study was collected between 2015 to 2016 and involved elderly women (ages ≥65 yeas) living in the Butanta district, Sao Paulo. The purpose of the study was identification of association between transcriptome and the osteo metabolism diseases phenotype, like osteoporosis, vertebral fracture and coronary calcification.
Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
Sex, Age
View SamplesInflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
No sample metadata fields
View SamplesWhile activation of canonical NF-?B signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-?B pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin ß receptor (LTßR)- and FN14-dependent p52 nuclear translocation, but not TNFa receptor (TNFR)-mediated, canonical NF-?B p65 nuclear translocation. Chemoproteomics identified cyclin dependent kinase 12 (CDK12) as the target of 919278. CDK12 inhibition by 919278, THZ1, or siRNA knock down all affect similar global transcriptional changes and prevent LTßR and FN14-dependent MAP3K14 (NIK) mRNA induction and subsequent protein accumulation. In addition, 919278 and THZ1 treatment reduce RNA Pol II CTD phosphorylation. This powerful approach of coupling a phenotypic screen with chemoproteomics revealed a novel regulatory pathway of the non-canonical NF-?B pathway that could serve as a therapeutic target in autoimmunity and cancer. Overall design: There are TWEAK stimulated and unstimulated conditions, 4hr and 24hr time points. 7 treatments (DMSO, BIO0702697, BIO0919278, BIO032202, NTsiRNA, siRNAs523626, siRNAs523629) in duplicates. In total, 56 sample were sequenced and analyzed.
CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling.
Cell line, Treatment, Subject, Time
View SamplesPhysical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection.
Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection.
No sample metadata fields
View Samples