Xue Y P, Ji X Y, Yang L, Liu H R, Sheng Y J, Dai X X, Xi Y J, Liu J C, Shi J, Xie T, Zhang Y S, Ma J W, Dong J
Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhonghua Yi Xue Za Zhi. 2018 Jan 30;98(5):340-345. doi: 10.3760/cma.j.issn.0376-2491.2018.05.005.
To investigate the correlation between nucleolus spindle-related protein 1 (NUSAP1) and malignant progression and prognosis of human glioblastoma multiforme (GBM). RT-PCR and immunohistochemical technique were applied to analyze NUSAP1 expression level in GBM surgical specimens. Correlations between NUSAP1 expression and molecular classification and survival of patients with GBM were also investigated in TCGA database. The gene silencing technique was used to silence NUSAP1 expression in U87 cells, CCK-8 assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle changes, and in vivo tumorigenicity was evaluated after NUSAP1 silencing in tumor-bearing mice. NUSAP1 expression level in GBM was higher than that in non-tumor brain tissue. Survival curve analysis showed that the survival time of GBM patients with high NUSAP1 expression decreased significantly (<0.01). NUSAP1 expression was relatively lower in mesenchymal and neural molecular subtypes of GBM, when compared with the other two molecular subtypes. And it was closely related with specific genetic aberrations (such as PTEN loss and IDH1 mutation). Silencing NUSAP1 inhibited G2/M cell cycle progression of GBM cells, and inhibited cell proliferation both in vitro and in vivo. Expression of NUSAP1 is closely related to progress and prognosis of GBM, and can be a biomarker reflecting GBM prognosis and act as a therapeutic target with potential clinical application value.
探讨核仁纺锤体相关蛋白1(NUSAP1)与人类多形性胶质母细胞瘤(GBM)恶性进展及预后的相关性。应用逆转录-聚合酶链反应(RT-PCR)和免疫组化技术分析GBM手术标本中NUSAP1的表达水平。还在癌症基因组图谱(TCGA)数据库中研究了NUSAP1表达与GBM患者分子分类及生存的相关性。采用基因沉默技术沉默U87细胞中NUSAP1的表达,使用细胞计数试剂盒-8(CCK-8)检测细胞增殖,采用流式细胞术检测细胞周期变化,并在荷瘤小鼠中沉默NUSAP1后评估体内致瘤性。GBM中NUSAP1的表达水平高于非肿瘤脑组织。生存曲线分析表明,NUSAP1高表达的GBM患者生存时间显著缩短(< 0.01)。与其他两种分子亚型相比,GBM的间充质和神经分子亚型中NUSAP1表达相对较低。并且它与特定的基因畸变(如PTEN缺失和异柠檬酸脱氢酶1(IDH1)突变)密切相关。沉默NUSAP1可抑制GBM细胞的G2/M期细胞周期进程,并在体外和体内抑制细胞增殖。NUSAP1的表达与GBM的进展和预后密切相关,可作为反映GBM预后的生物标志物,并作为具有潜在临床应用价值的治疗靶点。