MRNA-Integrative multi-omics survey of effects carbon-based engineered nanomaterials on lung derived cell-lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Greco Dario
PROVIDER: E-MTAB-6396 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In this study we exposed three human lung derived cell lines to sublethal dosages of nanomaterials for a limited amount of time. For the first time, we assessed the simultaneous effects of nanomaterials exposure on three distinct molecular layers along with their interactions in the determination of the MOA of 10 carbon based nanomaterials. By performing an integrative analysis we provide here a complete picture of the interaction between regulatory factors (DNA methylation and miRNAs) and mRNA deregulation subsequent to exposing different cellular systems to different nanomaterials.
2018-05-19 | E-MTAB-6397 | biostudies-arrayexpress
Project description:In this study we exposed three human lung derived cell lines to sublethal dosages of nanomaterials for a limited amount of time. For the first time, we assessed the simultaneous effects of nanomaterials exposure on three distinct molecular layers along with their interactions in the determination of the MOA of 10 carbon based nanomaterials. By performing an integrative analysis we provide here a complete picture of the interaction between regulatory factors (DNA methylation and miRNAs) and mRNA deregulation subsequent to exposing different cellular systems to different nanomaterials.
2018-05-19 | E-MTAB-6406 | biostudies-arrayexpress
Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response. Primary human aortic endothial cells (HAECs) were grown in 6 well plates (in 2 ml of medium) until they were >80% confluent by visual inspection. Daily media changes allowed continued growth for HAECs that demonstrate contact inhibition. The cells were then incubated with nanomaterials: surface modified SiO2 with worm and sphere goemetries (the spheres were 200 nm in diameter and the worm's cylindrical diameter 200 nm and the length was ~ 1000 nm); and PAMAM dendrimers with different surface charges (G3.5-COOH are negative and G4-NH2 are positive). RNA was collected after 4 and 24 hrs (one SiO2 worm sample was at 1.5 hrs due to space available on the 4-pack microarrays). Triplicate biological samples (indicated by the 'a', 'b', and 'c' designations in the sample names) were evaluated for gene expression changes by microarray analysis.
2013-12-20 | E-GEOD-35142 | biostudies-arrayexpress
Project description:Nanomaterials have lots of promising applications, and concern has risen about their impact to human health. Here, we have analyzed the genome-wide DNA methylation changes associated to the exposure to reduced graphene oxide (rGO) in human lung epithelial cells. Six conditions were assayed, with two technical replicates per condition (12 arrays in total): control, 1 and 10 µg/mL of rGO for 15 or 30 days of exposure.
2019-09-16 | E-MTAB-7719 | biostudies-arrayexpress
Project description:The increasing number of biological applications for black phosphorus (BP) nanomaterials has precipitated considerable concern about their interactions with physiological systems. Here, we demonstrate the adsorption of plasma protein onto BP nanomaterials and the subsequent immune perturbation effect on macrophages. Using liquid chromatography tandem mass spectrometry, we discovered that BP nanosheets (BPNSs) were able to bind 23.3 percent of immune proteins from plasma, while BP quantum dots (BPQDs) bound 41.8 percent of immune proteins. In particular, the protein corona dramatically reshaped BP nanomaterial-corona complexes, influenced cellular uptake, activated the NF-κB pathway and even increased cytokine secretion by 2-5-fold. BP nanomaterials induced immunotoxicity and immune perturbation in macrophages in the presence of a plasma corona. These findings offer important insights into the development of safe and effective BP nanomaterial-based therapies.
2018-05-18 | PXD009645 | Pride
Project description:The experiment was aimed at identification of genes whose expression is upregulated in human colon cancer C85 cells during the process of establishment of methotrexate-induced senescence.
2011-08-23 | E-MEXP-3018 | biostudies-arrayexpress
Project description:There is little in vitro data available on long-term effects of TiO2 exposure. Such data are im-portant for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms i.e. apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analysed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This cor-responded with an induced expression of key apoptotic proteins i.e. BAD and BAX, and an ac-cumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins in-volved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.
2021-07-15 | PXD025423 | Pride
Project description:Background: Castration-resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications. Methods: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 castration-resistant prostate cancers and 7 advanced tumors by array-CGH and gene expression microarrays. The genome-wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional dataset of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells. Results: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non-cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation. Conclusions: The DNA / RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target. [1] Gene expression levels from 13 samples were measured using Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Sample processing and labeling were done according to the protocol provided by Affymetrix. Three micrograms of total RNA from each sample was used for the initial one-cycle cDNA synthesis. Arrays were scanned immediately after staining using a GeneChip scanner (Affymetrix). [2] aCGH was performed from 18 prostate cancer samples using 44K arrays by Agilent Technologies. Male genomic DNA (catalog number G1471, Promega, Madison, WI) was used as reference in all hybridizations. [3] Gene expression changes following FAM110B silencing in LNCaP prostate cancer cells (48 h: pooled FAM110B siRNA vs. Scrambled siRNA; 72 h: FAM110B siRNAs 1 - 4 and pooled siRNA vs. Scrambled siRNA) and ectopic FAM110B over-expression in both RWPE-1 and LNCaP cells (FAM110B-pEGFP vs. pEGFP, 48 h) were analyzed. The raw data for these Samples are available in the 'GSE28403_LNCaP_RWPE-1_Raw_Data.txt' file, which is linked to this record as a supplementary file.
2011-08-28 | E-GEOD-28403 | biostudies-arrayexpress
Project description:Retinoic acid (RA) triggers growth-suppressive effects in tumor cells and therefore RA and its synthetic analogs have great potential as anti-carcinogenic agents. RA effects are mediated by retinoic acid receptors (RARs), which regulate gene expression in an RA-dependent manner. To define the genetic network regulated by RARs in breast cancer cells, we identified RAR genomic targets using chromatin immunoprecipitation and expression analysis in a model breast cancer cell line MCF-7. Furthermore, we identified genomic binding sites for two putative RAR coregulators FoxA1 and GATA3. Keywords: ChIP-Chip Analysis This series contains ChIP-Chip raw data for four transcription factors (RARA, RARG, FoxA1 and GATA3) in MCF-7 cells. All the experiments are done in triplicates. We mapped the binding sites of RARA, RARG and GATA3 in the bacterial artificial chromosome (BAC) transgenic MCF7 cells in which we tagged the transcription factors with a modified LAP (localization and affinity purification) tag containing green fluorescent protein (GFP). Goat anti-GFP (raised against His-tagged full-length eGFP and affinity-purified with GST-tagged full-length eGFP) was used to perform ChIP experiments in those transgenic lines. To map the binding sites of RARs, MCF7 Cells were hormone-deprived for 3 days and then were treated with 100 nM AM580 (RARA-selective agonist) or 100 nM CD437 (RARG-selective agonist) for 1 hour at 80% confluence. FoxA1 binding sites were mapped using goat anti-FoxA1 antibodies (Abcam: ab5089). Control data include Input from MCF-7 cells. ChIP-Chip experiments with eGFP antibody in wide type MCF-7 cells are used to control eGFP antibody non-specific binding.
2009-03-16 | E-GEOD-15244 | biostudies-arrayexpress
Project description:We have devised a technology that enables chromatin immunoprecipitation (ChIP) experiments in cultured human cells by circumventing both the laborious production of protein-specific antibodies and the optimization of crosslinking/immunoprecipitation conditions for each protein. Our approach utilizes bacterial artificial chromosomes (BACs) to physiologically express chromatinbinding proteins fused to epitope tags that are recognized by widely available and highly specific antibodies. We demonstrate the robustness of our methodology for mapping chromatin binding sites of transcription factors. Keywords: ChIP-Chip Analysis This series contains ChIP-on-Chip data sets for three transcription factors (FOXA1 (Forkhead box A1), XBP1-S (spliced X-box binding protein 1) and VDR (Vitamin D receptor)) and control samples (INPUT) for partial of the human genome including chromosomes 4, 15, 18, and 20 in MCF7 cells. We mapped the binding sites of these three transcription factors in the BAC transgenic MCF7 cells in which we tagged the transcription factors with a modified LAP (localization and affinity purification) tag. Goat anti-GFP (raised against His-tagged full-length eGFP and affinity-purified with GST-tagged full-length eGFP) was used to perform ChIP experiments in those transgenic lines. For comparison, we also mapped FOXA1 and XBP1-S binding sites with the available antibodies against the endogenous proteins. Goat anti-FoxA1 (Abcam: ab5089) and goat anti-XBP1 (Santa Cruz Biotech: sc-7160X) were used in these studies. Independent biological triplicates were performed for each transcription factor, as well as the control (Input).
2010-05-25 | E-GEOD-10845 | biostudies-arrayexpress