肾细胞癌中Nusap1表达下降抑制细胞迁移.docxVIP

肾细胞癌中Nusap1 表达下降抑制细胞迁移，增殖和入侵 摘要. Nusap1是 一种微管结合蛋白，这种蛋白在有丝分裂和癌症中起着至关重要的作用。以往的研究已经论证了NUSAP1 在多种恶性肿瘤中表达是相对升高的. 然而, NUSAP1 在肾细胞癌RCC) 中的生物学作用尚不清楚。在这次研究中，我们首先做了 逆转录PCR(RT-PCR) 和western-blot分析来揭示NUSAP1 的表达在肾透明细胞癌（CCRCC）组织标本和此外，癌细胞株中是相对升高的。免疫组化分析显示 NUSAP1 明显上调，fuhrman分级(P0.001), 肿瘤大小 (P=0.016), 临床阶段 (P0.001) ， 远处转移 (P=0.023)。此外, NUSAP1的高表达和透明细胞癌患者的总生存时间密切相关 (P=0.006). 此外，我们研究肾癌细胞体外的生物学行为, 发现 NUSAP1 消耗抑制RCC细胞迁移, 增殖和侵袭, 诱导细胞凋亡，阻滞细胞周期。在我们研究的基础上,NUSAP1被确定为一个潜在的预后指标和肾癌患者的新的治疗靶点。 介绍 肾细胞癌（RCC） 是最常见的癌症，起源于肾实质, 约占所有成年肾恶性肿瘤的90%(1). 肾细胞癌的主要组织学亚型是肾透明细胞癌（RCC）约占肾细胞癌RCCs的70-80％, followed by papil-lary (10-20%), chromophobe (5%) and collecting duct (1%) subtypes (2). Globally, the incidence of kidney cancer is approximately 270,000 new cases and 116,000 deaths, annu-ally (3). Despite considerable improvements in the diagnosis and treatment of RCCs in recent years, nearly 20-30% of all patients present with metastasis at the time of initial diagnosis, and approximately 20% of RCC patients who undergo nephrec-tomy may suffer recurrence or metastasis of the disease (4).For these patients, the prognosis is extraordinarily poor and median survival is not more than one year (5). Therefore, it is of great necessity to investigate the underlying molecular mechanisms of the tumorigenesis and progression of RCC. Identifying more novel biomarkers is still required to promote early diagnosis, targeted therapy and prognosis evaluation. Nucleolar and spindle-associated protein 1 (NUSAP1) is a recently identified protein with a molecular weight of 55 kDa that plays a crucial role in spindle microtubule organiza-tion (6). NUSAP1 exhibits a cell cycle-dependent localization and is selectively expressed in proliferating cells. Its mRNA and protein expression levels reach a peak at the transition of G2 to mitosis and then rapidly decline after cell division (7). The depletion and overexpression of NUSAP1 in cells result in abnormal chromosome segregation, aberrant spindle assembly,defective cytokinesis, G