This SuperSeries is composed of the SubSeries listed below.
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line, Treatment
View SamplesWe used the microarray analysis to detail the gene expression profile from the leukemic cell line HL-60
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line
View SamplesIdentification of the all RNA species associated with DNMT1. Using a comparative genome-scale approach we identified and correlated the RNA species physically associated with DNMT1 and proximal to the annotated genes to the methylation status of the corresponding loci and expression levels of the respective genes. This comparative approach delineated the first -DNMT1 centered- 'epitranscriptome' map, a comprehensive map cross-referencing DNMT1-interacting transcripts to (i) DNA methylation and (ii) gene expression profile. Overall design: Relationship between DNMT1-RNA interactions, DNA methylation and gene expression
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesWe explored the transcriptional modification induced by CD99 transfection in the osteosarcoma cell lines SaOS-2 after 0, 7 and 14 days in differentiation medium.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesA subanalysis of the GIMEMA-MMY-3006 trial was performed to characterize treatment-emergent peripheral neuropathy (PN) in patients randomized to thalidomide-dexamethasone (TD) or bortezomib-TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade 2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed from 122 VTD-treated patients. The incidence of grade 2 PN was 35% in the VTD arm and 10% in the TD arm (p<0.001). PN resolved in 88% and 95% of patients in VTD and TD groups, respectively. Rates of complete/near complete response, progression-free and overall survival were not adversely affected by emergence of grade 2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD-induced PN.
Bortezomib- and thalidomide-induced peripheral neuropathy in multiple myeloma: clinical and molecular analyses of a phase 3 study.
Specimen part, Disease, Disease stage
View Samplesß1-integrin is the major ß-integrin subunit expressed in both lens epithelial and fiber cells. Our previous research indicated that ß1-integrin is essential for the maintenance of lens epithelial integrity and survival in late embryonic lens development (Simirskii et al, 2009). Lack of ß1-integrin in the lens will lead to severe micropthalmia and lack of lens in adult mice. In order to study the mechanisms involved, high throughput RNA sequencing (RNAseq) was performed to determine the genes that are differentially expressed between E15.5 wild type (WT) lenses and lenses that lack ß1-integrin expression due to the action of MLR10 CRE (ß1-cKO). The methodology used here is similar to the other RNAseq experiments that were previously performed in our lab (Manthey et al., 2014a and Audette et al, 2015) (Geo accession: GSE 49949 and GSE69940) . Meanwhile, the filtering criteria and processing procedures were also published (Manthey et al., 2014b). Compared to WT, 120 genes were found to be differentially expressed in ß1-cKO lenses. Moreover, bioinformatics tools (DAVID (the database for Annotation, Visulization and Integrated Discovery), and PANTHER (Protein Analysis through Evolutionary Relationship) classification system) as well as manual literature searching was applied for further data analysis. It showed that genes involved in EMT and stress-responses were differentially expressed in ß1-cKO compared to that of WT. Description of filtering criteria: To identify the differentially expressed genes, pair-wise qCML method exact tests with a Benjamini Hochberg false discovery rate correction greater than the threshold of P<0.05 was applied, which identified 5120 genes. As previously described (Manthey et al., 2014b), most of the genes differentially expressed between inbred C57Bl/6 <har> and mice with a mixed background were below a threshold of 2.5 fold change. Therefore, all differentially expressed genes with a less than 2.5 fold change were filtered out. Further, genes whose expression level were not high enough to be biologically significant were also filtered out, based on the RPMK (Reads per Kilobase per million reads) value. Any gene in the final list has RPKM greater that 2 in either WT or ß1-cKO samples, a value that corresponds to approximately 1 mRNA molecule per cell. By applying a combination of these filtering criteria, 120 differentially expressed genes were found, which could potentially elucidate the molecular connections between conditional deletion of ß1-intergrin from the lens and the observed phenotypic abnormalities. Manthey, A. L., Lachke, S. A., FitzGerald, P. G., Mason, R. W., Scheiblin, D. A., McDonald, J. H. and Duncan, M. K. (2014a) ''Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development'', Mech Dev 131: 86-110. Manthey, A. L., Terrell, A. M., Lachke, S. A., Polson, S. W. and Duncan, M. K. (2014b) ''Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis'', Genom Data 2: 369-374. Overall design: RNA-Seq comparison of C57Bl/6 <har> wild type controls and ß1-integrin conditional knockout lenses at E15.5, three biological replicates were used in each group
β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesHepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFN-alpha) and ribavirin. It achieves a sustained viral clearance in only 5060% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFN-alpha. In patients with a rapid virological response to treatment, pegIFN-alpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFN-alpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.
Interferon signaling and treatment outcome in chronic hepatitis C.
No sample metadata fields
View SamplesDynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB).
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Specimen part, Treatment
View Samples