Alternatively activated NUSAP1 promotes tumor growth and indicates poor prognosis in hepatocellular carcinoma.

Alternatively activated NUSAP1 promotes tumor growth and indicates poor prognosis in hepatocellular carcinoma.
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替代激活的 NUSAP1 促进肿瘤生长并表明肝细胞癌预后不良

DOI:
10.21037/tcr.2019.01.29
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发表时间:
2019-03
影响因子:
0.9
通讯作者:
Deng L
Deng L
中科院分区:
医学4区
文献类型:
--
作者:
Shi C;Xu H;Liu J;Zhong Y;Zhang X;Tong X;Zhang L;Li X;Deng L

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背景肝细胞癌(Hepatocellular carcinoma,HCC)是最常见的恶性肿瘤之一,死亡率高.参与HCC发生发展的关键基因尚不完全清楚。方法我们对来自6个独立HCC数据集的可用转录组数据进行了荟萃分析[5个数据集来自基因表达综合数据库(GEO),1个数据集来自癌症基因组图谱(TCGA)]。分析核仁和纺锤体相关蛋白1(NUSAP 1)表达水平与临床病理因素和生存时间的关系。建立两种有代表性的肝癌细胞模型,观察shNUSAP 1抑制NUSAP 1表达时肝癌细胞的增殖能力。结果基于GEO和TCGA数据库中的转录组和生存数据,NUSAP 1基因在HCC中显著上调。NUSAP 1在HCC中的高表达与肿瘤细胞分化程度、肿瘤分化程度及TNM分期、肿瘤细胞分化程度、肿瘤细胞分化程度及生存率等因素有关。此外,基于RNAseq数据的途径分析表明,NUSAP 1可以激活参与细胞增殖的基因的表达。下调NUSAP 1的表达可显著抑制SMMC-7721和Huh 7细胞的体外增殖。结论NUSAP 1可能作为HCC预后的候选标志物和未来治疗干预的靶点。
Background Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality. The key genes involved in initiation and development of HCC is not entirely clear. Methods We performed a meta-analysis of available transcriptome data from 6 independent HCC datasets [5 datasets from the Gene Expression Omnibus (GEO) and 1 dataset from The Cancer Genome Atlas (TCGA)]. The associations of the nucleolar and spindle-associated protein 1 (NUSAP1) expression level with clinicopathological factors and survival times were analyzed. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when NUSAP1 expression was inhibited by shNUSAP1. Results Based on the transcriptome and survival data in the GEO and TCGA databases, NUSAP1 gene was markedly upregulated in HCC. High expression of NUSAP1 in HCC is related to the iCluster1 molecular subgroup, poor survival, poor tumor differentiation and TNM stage. Additionally, pathway analysis based on RNAseq data suggested that NUSAP1 could activate the expression of genes involves in cell proliferation. Furthermore, downregulation of NUSAP1 expression could significantly inhibit the proliferation of SMMC-7721 and Huh7 cells in vitro. Conclusions Our study provides evidence that NUSAP1 may serve as a candidate prognostic marker and a target for future therapeutic intervention in HCC.
DOI: 10.18632/oncotarget.15604
发表时间: 2017-05-02
期刊: Oncotarget
影响因子: --
作者:
Gordon CA;Gong X;Ganesh D;Brooks JD
通讯作者: Brooks JD
NUSAP是一种与有丝分裂纺锤体组织有关的新型微管相关蛋白。
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