Objective: To investigate the correlation between nucleolus spindle-related protein 1 (NUSAP1) and malignant progression and prognosis of human glioblastoma multiforme (GBM). Methods: 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. Results: 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 (P<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. Conclusion: 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.
目的： 探讨核仁纺锤体相关蛋白(NUSAP1)表达与人脑多形性胶质母细胞瘤(GBM)恶性进展及临床预后间的相关性。 方法： 以RT－PCR和免疫组化技术分析NUSAP1在GBM手术标本的表达水平。在TCGA数据库中分析该基因表达与GBM患者分子分型、生存期的相关性。采用基因沉默技术封闭该基因在U87细胞表达，CCK－8实验检测细胞增殖，流式细胞术检测细胞周期变化，并行体内致瘤试验。 结果： 与非肿瘤对照脑组织标本相比，NUSAP1在GBM表达明显上调，生存曲线分析显示，NUSAP1高表达者生存期显著降低(P<0.01)，间质型和神经元型GBM NUSAP1表达相对低于其他两型，且显著受PTEN缺失和IDH1突变等特定基因畸变状态影响。敲除NUSAP1可抑制GBM肿瘤细胞周期G2/M进展和细胞增殖。 结论： NUSAP1表达与GBM进展和预后密切相关，是一个反映GBM预后的生物标志物，并具有潜在应用价值的治疗靶标。.
Keywords: Glioblastoma multiforme; Malignant progression; NUSAP1; Prognostic factor.