MM1S cells have been cultured under normoxic and hypoxic conditions, and gene expression profiling has been performed using the Affymetrix Human Genome U133 Plus 2.0 array.
Metabolic signature identifies novel targets for drug resistance in multiple myeloma.
Cell line
View SamplesMicroarray-based DNA methylation and gene expression profiling was carried out using a panel of prostate cancer cell lines (LNCaP-FGC, DU-145, and PC-3) and the control normal prostate RWPE1 cell line. The identification of prostate cancer-specific methylation markers was based on the following criteria: a difference in DNA methylation level () of at least 0.5, and at least a 2-fold difference in expression level between cancer and control cells. Using highly stringent selection criteria, we identified novel hypermethylated genes whose expression was silenced in prostate cancer cells.
EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.
Specimen part, Cell line
View SamplesYamoa is marketed and sold as a dietary supplement with anecdotal positive effects in asthma and hay fever. We determined that Yamoa (ground bark of Funtumia elastica tree) stimulated innate immunity in part by affecting gamma delta T cells. Yamoa had distinct priming effects, very similar to, but more robust than, that of lipopolysaccharide (LPS), on bovine, mouse and human gamma delta T cells. However, the optimal effect was dependent on the presence of accessory cells. Gene expression patterns in bovine gamma delta T cells and monocytes induced by Yamoa were very similar to those induced by ultrapure LPS, but the agonists in Yamoa did not signal entirely through TLR4. Yamoa stimulated human cells to produce cytokines involved innate protection. The bioactive component of Yamoa was delineated to a complex polysaccharide fraction (Yam-I). Intraperitoneal injection of Yamoa and very low doses of Yam-I in mice induced rapid increases peritoneal neutrophils directed by changes chemokine expression. Yamoa and Yam-I were effective as therapeutic treatments in mice with Salmonella enterica serotype Typhimurium (ST) induced enterocolitis that resulted in decreased bacterial counts in feces. This initial characterization of the immune stimulatory properties of polysaccharides derived from Yamoa suggests potential mechanisms for positive effects in asthma and that they have potential for application in infectious disease settings. .
Polysaccharides derived from Yamoa (Funtumia elastica) prime gammadelta T cells in vitro and enhance innate immune responses in vivo.
No sample metadata fields
View SamplesThe objective of this study is to identify gene signature associated with castration-refractory prostate cancer (CRPC) development. We carried out RNA-seq based transcriptome profiling using 45 prostate samples with various disease progression steps such as benign prostate hyperplasia (BPH), primary cancer of prostate (CaP), advanced CaP and CRPC. Via various statistical analyses, we identified significant gene set associated with each progression step and observed that AR was the only gene feature associated with all progression steps, indicating that AR is the crucial mediator of and has a diverse activity across the CaP progressions. Among the samples in this data set, there are 4 pairs of advanced CaP and CRPC samples, in which each pair was obtained from the same patient. Using these paired samples, we also determined differentially expressed genes between advanced CaP and CRPC, and performed comparative analysis of significant gene lists in matched sample pairs and in unpaired remained samples. By assessing expression difference between advanced CaP and CRPC groups, 309 and 182 genes were statistically significant in paired and unpaired samples, respectively (P < 0.001). When these two gene lists were compared, a total of 15 genes were common and applied to a number of downstream experimental assays. Overall design: RNA-seq data of 45 CRPC samples were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer''s protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x100 bp) using Hiseq-2000 (Illumina).
Transcriptomic features of primary prostate cancer and their prognostic relevance to castration-resistant prostate cancer.
Subject
View SamplesGlioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential.
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation.
No sample metadata fields
View SamplesThe study was designed to identify differential expressed genes between human oral cavity carcinoma cell lines with and without LDBI knockout Overall design: Three parental human oral cavity carcinoma cell lines were used as control, LDB1 was knocked out in the three parent cell lines to create KO cell lines.
LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer).
No sample metadata fields
View SamplesThere are clear phenotypic differences between Korean native pig (KNP) and Yorkshire (YS) breeds because of different interests for selection. YS has been artificially selected by industrial interests such as a growth rate and a lean meat production, however, KNP has been maintained as a regional breed by local interests such as a fat content in or between muscle and a disease resistance. A comparison of gene expression profile from a major tissue liver can reflect the overall effects of the artificial selection between the two pig breeds through long history. KNP (n=4) and YS (n=4) pigs were raised under the identical conditions. Global gene expression levels were measured in liver samples from these pigs using Affymetrix porcine genome array containing 23,937 probe sets. The clustering analysis based on the individual transcriptome data showed a clear separation between two breeds in the liver tissue. We collected hepato-transcriptome data including 11,993 genes fully detected from four independent samples either in KNP or in YS. Based on both minimum positive false discovery rate (less than 15%) and fold change (|FC| > 1.5), 160 differentially expressed genes (DEGs) were collected from the liver between the two breeds. The functional analysis of these DEGs indicated clear distinctions in intra- and extra-cellular structure, cell proliferation, membrane trafficking, glycolytic pathway, mitochondrial function, protein metabolism, and immune response. The functional characteristics based on the DEGs were useful indicators to explain the differences between these two breeds developed for the specific purposes each other. The hepatic DGEs indicate that the YS has been lost expressivity of genes not required for the fast growth but maintained expressivity of genes for lean muscle production. The tissue-wise gene expression profiles indicate that the liver could be a major place to make the economic distinction between these two pig breeds.
Differences in hepatic gene expression as a major distinguishing factor between Korean native pig and Yorkshire.
Age, Specimen part
View SamplesInhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of PDE10A activity would have significant effects on gene expression in the striatum. A comparison of the expression profile of PDE10A knockout (KO) mice and wild-type mice after chronic PDE10A inhibition revealed altered expression of 19 overlapping genes with few significant changes outside the striatum or after administration of a PDE10A inhibitor to KO animals. Chronic inhibition of PDE10A produced up-regulation of mRNAs encoding genes that included prodynorphin, synaptotagmin10, phosphodiesterase 1C, glutamate decarboxylase 1, and diacylglycerol O-acyltransferase and a down-regulation of mRNAs encoding choline acetyltransferase and Kv1.6, suggesting long-term suppression of the PDE10A enzyme is consistent with altered striatal excitability and potential utility as a antipsychotic therapy. In addition, up-regulation of mRNAs encoding histone 3 (H3) and down-regulation of histone deacetylase 4, follistatin, and claspin mRNAs suggests activation of molecular cascades capable of neuroprotection. We used lentiviral delivery of cAMP response element (CRE)-luciferase reporter constructs into the striatum and live animal imaging of 2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid (TP-10)-induced luciferase activity to further demonstrate PDE10 inhibition results in CRE-mediated transcription. Consistent with potential neuroprotective cascades, we also demonstrate phosphorylation of mitogen- and stress-activated kinase 1 and H3 in vivo after TP-10 treatment. The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease.
Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease.
Specimen part, Treatment
View SamplesTo understand epigenetic changes in the distal regulatory as well as proximal regions, we performed RNA-seq, MBD-seq, and H3K27ac ChIP-seq on gastric tissues and cell lines. Overall design: mRNA sequencing profiles of normal tissue (n), purified gastric cancer (sc), and cultured gastric cancer cell (dc) were generated by deep sequencing, in five samples from three patients (csc1, csc2, csc3) and two replicates (csc1_sc2, csc1_sc3), using Illumina GAIIx and HiSeq2000.
Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer.
No sample metadata fields
View SamplesThe pig could be a useful model to characterize molecular aspects determining several delicate phenotypes because they have been bred for those characteristics. The Korean native pig (KNP) is a regional breed in Korea that was characterized by relatively high intramuscular fat content and reddish meat color compared to other western breeds such as Yorkshire (YS). YS grew faster and contained more lean muscle than KNP. We compared the KNP to Yorksire to find molecular clues determining muscle characteristics. The comparison of skeletal gene expression profiles between these two breeds showed molecular differences in muscle. We found 82 differentially expressed genes (DEGs) defined by fold change (more than 1.5 fold difference) and statistical significance (within 5% of false discovery rate). Functional analyses of these DEGs indicated up-regulation of most genes involved in cell cycle arrest, down-regulation of most genes involved in cellular differentiation and its inhibition, down-regulation of most genes encoding component of muscular-structural system, and up-regulation of most genes involved in diverse metabolism in KNP. Especially, DEGs in above-mentioned categories included a large number of genes encoding proteins directly or indirectly involved in p53 pathway. Our results indicated a possible role of p53 to determine muscle characteristics between these two breeds.
Transcriptional alteration of p53 related processes as a key factor for skeletal muscle characteristics in Sus scrofa.
Age, Specimen part
View Samples