Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA microarray analysis of ∆scnAB in Streptomyces chattanoogensis L10

ABSTRACT: scnA (GenBank: ADX66464.1) and scnB (GenBank: ADX66465.1) are ABC transporters located in the biosysnthesis gene cluster of natamycin in Streptomyces chattanoogensis. The two genes are presumbly involved in natamycin efflux. Our goal of this expriment was to investigate the effect of scnA and scnB inactivation on the gene expression in the whole genome. In ∆scnAB there were a total of 219 genes displaying at least a two-fold change (P<0.05), including 89 genes with lower and 130 genes with higher expressions In this study, RNA isolated from ∆scnAB or wild type Streptomyces chattanoogensis L10, was used to acquire expression profiles of a total of 8,117 protein-coding genes in S. chattanoogensis L10, leading to the successful construction of different expression profiles between scnA and scnB deletion mutant and wild type S. chattanoogensis L10.

ORGANISM(S): Streptomyces chattanoogensis

SUBMITTER: TanJun Wang

PROVIDER: E-GEOD-73086 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.

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DNA microarray analysis of ∆scnAB in Streptomyces chattanoogensis L10

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