Combinatorial treatment of DNMT inhibitor and LSD1 inhibitor results in cell growth inhibition and reexpression of epigenetically silenced genes (gene expression)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Xiaojing Yang
PROVIDER: E-GEOD-41676 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-01 | E-GEOD-41754 | biostudies-arrayexpress
Project description:In order to understand the relationships between the human non-GCIMP glioblastoma subgroups, we performed computational analysis of human genomic data to predict the temporal sequence in which the driver events arise during tumorigenesis. The order of evolutionary events for non-GCIMP GBM is 1) chr 7 gain and loss of chr 10, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes such as NF1 loss or focal amplification of PDGFRα or EGFR. We then developed a computational methodology to identify the drivers of broad copy number changes, identifying PDGF-A (chr 7) and PTEN (chr 10) as driving the initial non-disjunction events. These predictions were validated using mouse modeling, showing PDGF-A is sufficient to induce PN-like gliomas that are enhanced by loss of Ink4a-Arf, Tp53 or Pten. Additional Nf1 loss converts PN to the MES subtype. Our findings suggest non-GCIMP GBMs arise as, and evolve from, a common proneural-like precursor. hGBM_sphere: Three different human GBM sphere lines expressing two different NF1-shRNAs or empty shRNA-control were generated by a lentiviral infection with the relevant pLKO.1 vectors. The total RNAs were obtained from the GBM sphere lines and the gene expression profile of the NF1-shRNA cells was then compared to the control cells. hGBM_rapamycin: Two human GBM sphere lines (TS543 and TS667) expressing the NF1-shRNAs were generated by a lentiviral infection with two different pLKO.1-NF1-shRNA vectors (two different target sequence; #2 and #5). The total RNAs were obtained from the NF1-shRNA lines treated with a 1nM rapamycin or 0.1% DMSO control for 5 hours and the gene expression profile was then compared between the both groups. Murine_gliomas: Murine brain tumors were generated by an injection of DF1 cells producing the relevant RCAS virus into newborn pups or adult mice brain. When mice presented any symptoms of disease, the mice were sacrificed and the brain tumor tissues were macroscopically dissected. Then total RNAs were extracted from the murine brain tumors or normal brain tissues and the gene expression profile was compared between various tumor types and/or normal brain tissues. In this study, two different RCAS-shNf1 (GR249 and GF249) and shp53 (R696 and mR696) was used for the generation of the murine brain tumors. Each RCAS vector has different structure but the target sequence against the Nf1 and p53 is same and similar knockdown effect was observed. Tumor grade were determined with the residual sections after a piece of tumor tissue were excised for the RNA extraction. The detail information of the experiment was described in the associated-publication. Murine_shere: Murine neurosphere lines were generated by a retroviral infection with the relevant RCAS viruses. The total RNAs were obtained from the murine neurosphere lines expressing the RCAS-shGL2, shNf1, shp53 or shNf1+shp53 and the gene expression profiles of the shNf1, shp53 or shNf1/p53 cells were then compared to the control shGL2 cells.
2014-04-03 | E-GEOD-45874 | biostudies-arrayexpress
Project description:The aim of the dataset was to identify genome-wide regulators of gene expression in early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) and Th2 (Act+IL4) polarising conditions. Total RNA from naive CD4+ T cells was compared to total RNA from cells cultured in the following three conditions: activating (antiCD3+antiCD28)+antiIL4+antiIFNG; activating (antiCD3+antiCD28)+IL12+antiIL4; activating (antiCD3+antiCD28) +IL4+antiIFNG. Samples from 3 biological replicates were analysed.
2015-11-20 | E-GEOD-71575 | biostudies-arrayexpress
Project description:Effects of EPA/DHA enriched high fat diets (HFD) compared to HFD-Corn oil after 8 weeks intervention on age/obesity induced sarcopenia. Results provides novel information on the signalling pathways regulated by EPA/DHA enriched HFD in delaying the onset of sarcopenia in C57Bl/6J mice compared to HFD-Corn oil. Four mice representing each diet group on the basis of body weight, plasma triglyceride and plasma cholesterol levels were selected for RNA isolation and microarray analysis. Total RNA from skeletal muscle of these selected animals was purified using the RNeasy® Plus Universal Mini kit (Qiagen Nordic, Sollentuna, Sweden) by following the manufacturer?s instruction carefully. The extracted RNA was quantified by NanoDrop 2000c UV-Vis Spectrophotometer (Thermo Scientific, USA) and the quality of the RNA was estimated by RNA 6000 Nano LabChip for Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, California, USA).
2016-05-31 | E-GEOD-76361 | biostudies-arrayexpress
Project description:Investigation of the role of miR-29 on transcriptional responses to Mycobacterium tuberculosis (MTB) infection in human dendritic cells using gain- and loss-of-function approaches and microarray expression profiling. We assessed the impact of miR-29 perturbation on mRNA expression levels before and after MTB infection in dendritic cells using cells collected from 4 unrelated individuals. Cells were transfected using either a miR-29a mimic or miR-29 family inhibitor before infection with H37Rv for 24 hours. Gene expression was profiled by array and 4 technical replicates were performed to confirm reproducibility.
2014-01-17 | E-GEOD-53143 | biostudies-arrayexpress
Project description:Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression. Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen. Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR. Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001). Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition. 9 paired samples of human myometrium treated with MPA (10-7M) or vehicle
2011-06-08 | E-GEOD-22961 | biostudies-arrayexpress
Project description:Exposure to ambient particulate matter (PM) significantly increases cardiovascular morbidity and mortality in the general population. We hypothesized that some components of PM can affect the gene expression patterns in the hearts of rats exposed for 3 months to filtered air (FA), coarse (CP; 2.5 < dp < 10 μm), fine (FP; dp ≤ 2.5 μm) or ultrafine (UFP; dp ≤ 0.18 μm) components of PM. The median diameters of CP, FP, and UFP were 3 μm, 0.7 μm and 0.07 μm, respectively. Exposures (n = 8 per group) were performed using a particle concentrator system in Riverside, California, an area with high ambient levels of photochemically derived gaseous and particulate pollutants. At the end of the exposure, hearts were subjected to gene expression profiling by using Illumina RatRef-12 bead chips and levels of malonaldehyde (MDA), a biomarker of oxidative stress, were measured. Applying fold ratio >1.5 (for both up- and downregulated genes), we found three genes in the CP and nine genes in the UFP groups with significantly changed expression, compared with FA. No significant changes in gene expression patterns were observed in the FP group. In the UFP group, thioredoxin-interacting protein (Txnip), a negative regulator of an antioxidant enzyme thioredoxin, and cytochrome P450 (Cyp2e1), an enzyme involved in the metabolism of foreign substances, demonstrated significant up-regulation (fold ratios 1.79 and 1.57, respectively, with false discovery rate, FDR < 0.05). In the CP group, there was also a trend towards increased Txnip expression (fold ratio 1.43, FDR > 0.05) and significant increase in the Cyp2e1 expression (fold ratio 1.79, FDR < 0.05). Changes in the Txnip and Cyp2e1 expression showed statistically significant positive correlation to each other (p < 0.0009) and were confirmed by real-time PCR. In addition, Txnip and Cyp2e1 expression demonstrated statistically significant moderate correlation with the levels of MDA in the heart. Up-regulation of both Cyp2e1 and Txnip are observed in hearts of patients with certain cardiac diseases. Therefore, chronic exposure to CP and UFP directly affects expression of disease-relevant genes in the myocardium. Analysis was performed on 32 microarrays (eight microarrays in each group). After five chips with poor hybridization signals were removed, the final analysis included 27 microarrays (seven miocroarrays in the FA group, six microarrays in the CP group, six microarrays in the FP group and eight microarrays in the UFP group). The Bioconductor Lumi package was used to preprocess gene chip data with default settings (Du et al. 2007; Lin et al. 2008). Probes with all samples “Absent” (lower or around background levels) were removed from further analysis. After filtering the signals, 11,657 probes on the microarray (from a total of 22,226 probes) were kept for further analysis. To identify differentially expressed genes, we applied routines implemented in the Limma package (Linear model for microarray data) to fit linear models to normalized expression values. The variance used in the t-score calculation was corrected by an empirical Bayesian method (Smyth 2004). Genes with significantly changed expression (fold ratio >1.5 for both up- and downregulated genes) were selected. The gene list was further filtered by FDR (false discovery rate) of <0.05 and <0.25, which indicate that no more than 5% and 25% of all listed genes are false positives (an assumption that is not offered by a traditional p value-based analysis).
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2012-12-28 | E-GEOD-43135 | biostudies-arrayexpress
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