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首页> 外文期刊>Neoplasma: Journal of Experimental and Clinical Oncology >Targeting genes and signaling pathways of transcriptional suppressor ZHX2 in hepatocellular carcinoma: a Chromatin Immunoprecipitation-sequencing (ChIP-seq) investigation
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Targeting genes and signaling pathways of transcriptional suppressor ZHX2 in hepatocellular carcinoma: a Chromatin Immunoprecipitation-sequencing (ChIP-seq) investigation

机译：肝细胞癌转录抑制λ2的靶向基因和信号通路：染色质免疫沉淀序列测序（芯片-SEQ）调查

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摘要

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The unclear underlying molecular mechanisms could provide important theoretical basis for prevention and control of HCC. In this study, chromatin immunoprecipitation-sequencing (ChIP-seq) was performed to analyze the binding sites of zinc fingers and homeoboxes 2 (ZHX2) and its genome-wide target genes, and bioinformatics was used to analyze their gene transcription regulation network. Immunohistochemistry detected the ZHX2 expression in HCC, and its association with clinicopathological characteristics of HCC. Results of RT-PCR and western blot showed that the ZHX2 expression in HepG2 cells was obviously lower compared to normal liver cells. ZHX2 could be amplified in ChIP products and ChIP-seq revealed there were 232 genes binding in promoter regions. GO function analysis revealed these genes were mainly associated with biological processes (BP), cellular components (CC), and molecular functions (MF). In addition, PTEN was found enriched in certain biological functions in BP analysis. Then, four pathways of these genes based on Kyoto Encyclopedia of Genes and Genomes (KEGG) were found p<0.05. Last immunohistochemistry analysis showed the rates of ZHX2 and PTEN expression in paracancerous tissues were both significantly higher than in the HCC tissues (p=0.042; p<0.001), with negative correlations with AFP values (r=-0.246, p=0.040; r=-0.263, p=0.028). Further, PTEN expression was positively correlated with the differentiation level in HCC tissues (r=0.267, p=0.025). Spearman correlation analysis revealed that the expression profiles of ZHX2 and PTEN were positively correlated in HCC tissues (r=0.258, p=0.031). This study is the first to use ChIP-seq technology to analyze the specific regulatory mechanisms of the transcription suppressor ZHX2 in the context of HCC at the genome level.
机译：肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一。目前不明确的潜在的分子机制可以为预防和控制HCC提供重要的理论依据。在该研究中，进行染色质免疫沉淀序列测序（CHIP-SEQ）以分析锌指和家用毒弹2（ZHX2）的结合位点及其基因组靶基因，并使用生物信息学分析其基因转录规则网络。免疫组织化学检测到HCC中的ZHX2表达及其与HCC临床病理特征的关联。 RT-PCR和Western印迹的结果表明，与正常肝细胞相比，HepG2细胞中的ZHX2表达明显低。 ZHX2可以在芯片产品中扩增，芯片SEQ显示出在启动子区中有232个基因结合。 GO功能分析显示这些基因主要与生物过程（BP），细胞组分（CC）和分子官能（MF）相关。此外，在BP分析中发现PTEN在某些生物学功能中富集。然后，发现基于京都基因和基因组（Kegg）的这些基因的四种途径P <0.05。最后的免疫组织化学分析显示臀部组织中的ZHX2和PTEN表达的速率显着高于HCC组织（P = 0.042; P <0.001），具有与AFP值的负相关（R = -0.246，P = 0.040; r = -0.263，p = 0.028）。此外，PTEN表达与HCC组织中的分化水平正相关（R = 0.267，P = 0.025）。 Spearman相关性分析显示，ZHX2和PTEN的表达谱在HCC组织中呈正相关（r = 0.258，p = 0.031）。本研究是第一个使用芯片-SEQ技术来分析在基因组水平的HCC的背景下转录抑制剂ZHX2的特定调节机制。

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  • 作者

    Lv Z.; He R.; Huang M.; Zhao G.; Ma J.; Chen G.;

  • 作者单位

    Guangxi Med Univ Affiliated Hosp 1 Dept Pathol Nanning 530021 Guangxi Zhuang Peoples R China;

    Guangxi Med Univ Affiliated Hosp 1 Dept Med Oncol Nanning 530021 Guangxi Zhuang Peoples R China;

    Guangxi Med Univ Affiliated Hosp 1 Dept Pathol Nanning 530021 Guangxi Zhuang Peoples R China;

    Guangxi Med Univ Affiliated Hosp 1 Dept Pathol Nanning 530021 Guangxi Zhuang Peoples R China;

    Guangxi Med Univ Affiliated Hosp 1 Dept Med Oncol Nanning 530021 Guangxi Zhuang Peoples R China;

    Guangxi Med Univ Affiliated Hosp 1 Dept Pathol Nanning 530021 Guangxi Zhuang Peoples R China;

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  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    hepatocellular carcinoma; HCC; transcription repressor; ZHX2; ChIP-Seq;

    机译：肝细胞癌;HCC;转录阻遏物;ZHX2;芯片 - SEQ;

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