23 research outputs found

    Association of polymorphisms in the heparanase gene (HPSE) with hepatocellular carcinoma in Chinese populations

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    <div><p>Abstract Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A log-additive model revealed significant correlations between the HPSE polymorphisms rs12331678 and rs12503843 and the risk of HCC in the overall samples (p = 0.0046 and p = 0.0055). When the analysis was stratified based on hepatitis B virus (HBV) carrier status, significant interactions between rs12331678 and rs12503843 and HBV were observed. Conditional logistic regression analysis for the independent effect of one significant SNP suggested that rs12331678 or rs12503843 contributed an independent effect to the significant association with the risk of HCC, respectively. Our findings suggest that the SNPs rs12331678 and rs12503843 are HCC risk factors, although the potential functional roles of these two SNPs remain to be fully elucidated.</p></div

    Roles of caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and the NOD-like receptor family pyrin domain containing 3 (NLRP3) in EHEC O157:H7-induced IL-1β production.

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    <p>THP-1 cells were transfected with control siRNA or siRNA specific to caspase-1, ASC, or NLRP3, respectively. After 48 h, cells were infected with EDL933, Δ<i>ehxA</i>, ΔpO157, and Δ<i>ehxA</i>/pehxA, respectively. (A) Knockdown of caspase-1, ASC, and NLRP3, was assayed by Western blotting. (B) Cell culture supernatants were collected 4 h after infection and subjected to IL-1β ELISA. Results represent the mean ± S.D. of three independent experiments. Significant differences (**<i>p</i><0.01, *<i>P</i><0.05) were indicated. n.s., no significant differences (<i>P</i>>0.05).</p

    MiR-410 Is Overexpressed in Liver and Colorectal Tumors and Enhances Tumor Cell Growth by Silencing FHL1 via a Direct/Indirect Mechanism

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    <div><p>FHL1 is an important tumor-suppressor that is downregulated in multiple tumors by unknown mechanisms. We demonstrated that miR-410 specifically targets the 3′UTR of FHL1. Furthermore, using DNA bisulfite modification and sequencing experiments, we demonstrated that the FHL1 promoter is hypermethylated in cancer cells. FHL1 methylation is increased upon miR-410 expression, suggesting that the regulation of FHL1 by miR-410 occurs by a dual mechanism. Using chromatin immunoprecipitation assays, we observed that miR-410 overexpression results in the increased binding of DNMT3A at the FHL1 promoter, which could explain how miR-410 regulates FHL1 methylation. Importantly, <i>in vitro</i> and <i>in vivo</i> results suggest that miR-410 may have oncogenic properties. Furthermore, both miR-410 and DNMT3A are upregulated in clinical human liver and colorectal tumors cancers. Our results suggest that miR-410 may function as an oncomiR and are consistent with its key function in regulating FHL1 in certain digestive system cancers.</p></div

    Pro-IL-1β and mature IL-1β in cell extract and supernatant as visualized by Western blotting.

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    <p>At 4 h after infection, pro-IL-1β and IL-1β in cell extracts (CX) and supernatants (SN) were visualized by Western blot analysis.</p

    Construction of the mutant strains.

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    <p>(A) The genes <i>ehx</i> and <i>ecf</i> were detected in EDL933 but not in ΔpO157. Lane M: marker; Lanes 1 and 3: EDL933; Lanes 2 and 4: ΔpO157 mutant. (B) Comparison of genomic DNA of EDL933 and ΔpO157 using PFGE of <i>Xba</i>I-digested. Lane M: marker; Lane 1: EDL933; Lane 2: ΔpO157 mutant. (C) Using primer <i>ehxA</i>-3,4, EDL933 was amplified as a ≈3.3 kb fragment. Δ<i>ehxA</i> and Δ<i>ehxA</i>/pehxA were amplified as a reduced fragment to ≈1.6 kb. Using primer <i>ehxA-</i>5,6, Δ<i>ehxA</i> showed no PCR product. EDL933 and Δ<i>ehxA</i>/pehxA were amplified as a ≈360 bp fragment. Lane 1: EDL933; Lane 2: Δ<i>ehxA</i>; Lane 3: Δ<i>ehxA</i>/pehxA.</p

    Expression of inflammasome components in differentiated THP-1 cells.

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    <p>Differentiated THP-1 cells were left untreated or were infected with EDL933 or Δ<i>ehxA</i>. They were then lysed over 4 h postinfection. mRNA expression of selected genes was analyzed using RT-PCR.</p

    Cytotoxicity of human macrophages as indicated by the release of lactate dehydrogenase (LDH).

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    <p>Differentiated THP-1 cells were exposed to different bacterial strains (EDL933, ΔpO157, Δ<i>ehxA</i>, Δ<i>ehxA</i>/pehxA) for 2 and 4 h. The release of LDH was assessed at specific times during incubation. Data are shown as mean ± S.D. of experiments performed in triplicate. Significant differences (* <i>P<</i>0.05) are indicated. n.s., no significant differences (<i>P</i>>0.05).</p
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