Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived brain transcriptome profiling (RNA-seq) in neuropathic region specific Gaucher mouse brain compared with WT and Isofagamine treated mice of the same age and background and secondly to identify the DEmiRNA associated with the DEmRNA before and after treatment This will give us some insights to see if miRNA is also involved in the the regulation of the expression of the genes involved in the disease process before and after treatment. Methods: 42-45 days old 4L;C*, wild-type (WT) and Isofagamine treated 4L;C* mouse brain were generated by deep sequencing, in triplicate, using IlluminaHiseq. The sequence reads that passed quality filters were analyzed at the gene level with two methods: Burrows–Wheeler Aligner (BWA) followed and TopHat followed by DESeq. qRT–PCR validation was performed using TaqMan and SYBR Green assays Overall design: Regional brain mRNA profiles of ~42 -days old wild type (WT) and 4L;C* an d Isofagamine treated mice were generated by deep sequencing, in triplicate, using IlluminaHi Seq.
Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.
No sample metadata fields
View SamplesSkeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training
Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes.
Age
View SamplesIntroduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERa) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option. Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor). Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach. Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors. Overall design: 46 samples, 28 days post treatment
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.
Cell line, Treatment, Subject, Time
View SampleslncRNAs not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in MDS remains unclear to date.
A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesHeart failure remains a major unmet clinical need and current therapies targeting neurohomonal and hemodynamic regulation have limited efficacy. We report that pharmacological activation of the transcriptional repressor REV-ERBa prevents expression of a pathological gene program and cardiomyocyte hypertrophy. In vivo, REV-ERBa agonism prevents development and halts progression of heart failure in mouse models. Thus, modulation of gene networks by targeting REV-ERBa represents a novel approach to heart failure therapy. Overall design: We performed RNAseq on NRVM at baseline and after PE stimulation (4 hr and 48 hr) in the presence or absence of SR9009 (SR or Veh were given 24 hr prior to PE).
REV-ERBα ameliorates heart failure through transcription repression.
No sample metadata fields
View SamplesUnsupervised hierarchical clustering revealed a strong similarity in gene modulation resulting from either compound treatment or BRAF ablation mediated by RNA interference relative to DMSO-treated control samples .
Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Specimen part, Cell line
View SamplesThe association of DNA CpG methylation (or its absence) with occupancy of histone post translational modifications has hinted at an underlying crosstalk between histone marks and DNA methylation in patterning the human methylome, an idea supported by corresponding alterations to both histone marks and DNA methylation during malignant transformation. This study investigated the framework by which histone marks influence DNA methylation. Using RNAi in a human pluripotent embryonic carcinoma cell line we depleted essential components of the histone modifying complexes that establish the posttranslational modifications H3K4me3, H3K27me3, and H2AK119ub, and we assayed the impact of the subsequent loss of these marks on the DNA methylome. Absence of H2AK119ub resulted predominantly in hypomethylation across the genome. Removal of H3K4me3 or, surprisingly, H3K27me3 caused CpG island hypermethylation at a subset of loci. Intriguingly, many promoters were co-regulated by all three histone marks, becoming hypermethylated with loss of H3K4me3 or H3K27me3 and becoming hypomethylated with depletion of H2AK119ub, and many of these co-regulated loci were among those that are commonly, aberrantly hypermethylated in cancer.
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Specimen part, Cell line
View SamplesWe have identified the transcription factor forkhead box protein F2 (Foxf2) to be upregulated in its expression during the EMT process and studied its functional contribution to EMT by siRNA-mediated knockdown in NMuMG cells treated for 4 days with TGFbeta followed by mRNA-sequencing. Our analysis revealed a dual role of Foxf2 during TGFbeta-induced EMT in promoting apoptosis while inducing cell junction breakdown and migration. Overall design: mRNA sequencing of NMuMG/E9 cells transfected with control siRNA or Foxf2 specific siRNA and treated with TGFbeta for 4 days
Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by promoting apoptosis yet enabling cell junction dissolution and migration.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells.
Specimen part, Cell line
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