23 research outputs found

    Boxplots showing the effect of <i>WDR5</i> knockdown on cell viability in the MCF7 breast cancer cell line.

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    <p>Boxplots showing the effect of <i>WDR5</i> knockdown on cell viability in the MCF7 breast cancer cell line.</p

    <i>WDR5</i> Expression Is Prognostic of Breast Cancer Outcome

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    <div><p>WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of <i>WDR5</i> gene expression on breast cancer survival. Our findings reveal that <i>WDR5</i> over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with <i>WDR5</i> are enriched with “cellular development, gene expression, cell cycle” signallings. Knocking down <i>WDR5</i> in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of <i>WDR5</i> expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting <i>WDR5</i> once such a regimen is available.</p></div

    Kaplan-Meier plots of breast cancer patient survival based on WDR5 expression.

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    <p>Plots represent DFS from the main analysis of A) GSE24450, B) GSE1456, and C) GSE4922 data sets, and subgroup analysis of D) anthracycline treated and E) untreated tumours from GSE24450 data. The p value and hazard ratio (HR) are shown in each subplot. The number of patients is shown in the brackets in the legends. Data on the breast cancer specific death over 10 years using GSE24450 are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124964#pone.0124964.s001" target="_blank">S1 Fig</a>.</p

    Kaplan-Meier plot of breast cancer patient survival based on <i>WDR5</i> expression using MTCI BreastMark.

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    <p>Plots represent the DFS. n = 1378, number of events = 715, Hazard ratio = 1.297 (1.119–1.502), score (log rank) test = 12.03 on 1 df, p = 0.0005236.</p

    Summarized statistics of the association between <i>WDR5</i> gene expression and breast cancer patient survival.

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    <p>The p value and hazard ratio (HR) of tumours over-expressing <i>WDR5</i> are depicted below. In the ‘Subgroup’ column, ‘Anthr+’ and ‘Anthr-’ labels represent the anthracycline treated and untreated group respectively, and ‘main’ means all samples are used in the analysis. The number of patients is shown in the ‘Sample’ column, with the number of events listed in the brackets.</p><p>Summarized statistics of the association between <i>WDR5</i> gene expression and breast cancer patient survival.</p

    Transcriptome analysis of <i>Corynebacterium glutamicum</i> in the process of recombinant protein expression in bioreactors

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    <div><p><i>Corynebacterium glutamicum</i> (<i>C</i>. <i>glutamicum</i>) is a favorable host cell for the production of recombinant proteins, such as important enzymes and pharmaceutical proteins, due to its excellent potential advantages. Herein, we sought to systematically explore the influence of recombinant protein expression on the transcription and metabolism of <i>C</i>. <i>glutamicum</i>. Two <i>C</i>. <i>glutamicum</i> strains, the wild-type strain and an engineered strain expressing enhanced green fluorescent protein (EGFP), were cultured in parallel in 5-L bioreactors to study the change in metabolism in the process of EGFP expression. The results revealed that EGFP expression had great effects on the growth and metabolism of <i>C</i>. <i>glutamicum</i> and contributed to metabolism-like anaerobic conditions as follows: glycolysis was enhanced, the TCA cycle was shunted, and Glu, Val, Met, lactate and acetate were accumulated to produce sufficient ATP for EGFP production and transfer. Many differentially expressed genes related to ribosomal protein, transcriptional regulators, and energy metabolism were found to be expressed in the presence of EGFP, laying the foundation for identifying genomic loci to change the flow of the host cell metabolism to improve the ability of expressing foreign proteins in <i>C</i>. <i>glutamicum</i>.</p></div

    Biomass, CDW and sugar concentration of <i>C</i>. <i>glutamicum</i> BZH 001 and <i>C</i>. <i>glutamicum</i> EGFP during 48 h of fermentation.

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    <p>Biomass, CDW and sugar concentration of <i>C</i>. <i>glutamicum</i> BZH 001 and <i>C</i>. <i>glutamicum</i> EGFP during 48 h of fermentation.</p

    GO classification and pathway enrichment.

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    <p>A: GO classification of different expression genes. B: Pathways enrichment of different expression genes.</p
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