Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The anti-tumor core molecular targets of TSA in cholangiocarcinoma

ABSTRACT: Firstly our study demonstrated that TSA can inhibits cell proliferation, induces cell apoptosis and cell cycle arrest in CCA cell lines in vitro. To identify the target transcripts of TSA to suppress CCA tumorigenesis, mRNA expression profiles were determined by microarray analysis. We chose TFK-1 cells treated by TSA in indicated concentration (IC50) 48 hours for the microarray. Then we found out TACC3 was downregulated, and demonstrated that TACC3 was high expression and may played a role as an target of TSA in inhibiting CCA cells proliferation and migration via in vitro and vivo experiments. We chose TFK-1 cells treated by TSA in indicated concentration (IC50) 48 hours as the experiment sample and without TSA as the control sample to do this microarray analysis for three times. Then regulated genes would be tested to investigate the potential roles in CCA tumorigenesis,

ORGANISM(S): Homo sapiens

SUBMITTER: wei yao

PROVIDER: E-GEOD-78867 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Whereas cloning mammals by direct somatic cell nuclear transfer has been successful using a wide range of donor cell types, neurons from adult brain remain M-bM-^@M-^\unclonableM-bM-^@M-^] for unknown reasons. Here we examined whether neurons from adult mice could be cloned, using a combination of two epigenetic approaches. First, we used a specific antibody to discover cell types with reduced amounts of a repressive histone mark - dimethylated histone H3 lysine 9 (H3K9me2) - and identified CA1 pyramidal cells in the hippocampus and Purkinje cells in the cerebellum as candidates. Second, reconstructed embryos were treated with trichostatin A (TSA), a potent histone deacetylase inhibitor. Using CA1 cells, cloned offspring were obtained at high rates, reaching 10.2% and 4.6% (per embryos transferred) for male and female donors, respectively. Cerebellar Purkinje cell nuclei were too large to maintain their genetic integrity during nuclear transfer, leading to developmental arrest of embryos. However, gene expression analysis using cloned blastocysts corroborated a high rate of genomic reprogrammability of CA1 pyramidal and Purkinje cells. Neurons from the hippocampal dentate gyrus and cerebral cortex, which had higher amounts of H3K9me2, could also be used for producing cloned offspring, but the efficiencies were low. A more thorough analysis revealed that TSA treatment was essential for cloning adult neuronal cells. This study demonstrated for the first time that adult neurons could be cloned by nuclear transfer. Furthermore, our data imply that reduced amounts of H3K9me2 and increased histone acetylation appear to act synergistically to improve the development of cloned embryos. Comparative gene expression analyses using blastocysts of cloned embryos were performed by microarray. Cloned embryos were produced with three different types of donor cells (neonatal Sertoli cells, CA1 pyramidal cells and Purkinje cells) and all cloned embryos were treated with Trichostatin A (TSA). Each embryos were cultured for 96 h and blastocysts derived from each donor cell types were subjected to gene expression microarray. For comparison of gene expression, the data sets of control sex- and genotype-matched embryos produced by in vitro fertilization and SCNT-derived blastocysts from cumulus cells treated with TSA from our previous paper (Inoue K. et al. Science 2010) were also used.

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The anti-tumor core molecular targets of TSA in cholangiocarcinoma

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