Nek7 is overexpressed in hepatocellular carcinoma and promotes hepatocellular carcinoma cell proliferation in vitro and in vivo.
Nek7 is overexpressed in hepatocellular carcinoma and promotes hepatocellular carcinoma cell proliferation in vitro and in vivo.
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Nek7在肝细胞癌中过表达并促进肝细胞癌细胞体外和体内增殖
DOI：
10.18632/oncotarget.7620
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Liu C
中科院分区：
文献类型：
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作者：
Zhou L;Wang Z;Xu X;Wan Y;Qu K;Fan H;Chen Q;Sun X;Liu C
NIMA 相关激酶 7 (Nek7) 是一种丝氨酸/苏氨酸激酶，通过有丝分裂纺锤体形成和胞质分裂参与细胞周期进程。在本研究中，我们研究了 Nek7 是否参与肝细胞癌 (HCC)。有趣的是，我们发现 Nek7 在 HCC 中比在肝组织中显着过度表达。在HCC患者中，Nek7的高表达与肿瘤数量、肿瘤直径、邻近器官侵犯、肿瘤分级和TNM分期显着相关。此外，Nek7 表达模式与稳定的细胞增殖标志物 Ki-67 的表达模式显示出密切的关系。更重要的是，Nek7表达水平较高的患者5年生存率显着较低。同样，HCC 细胞系中的 Nek7 表达显着高于正常肝细胞系。通过使用慢病毒介导的Nek7干扰方法沉默Nek7，HCC细胞系的生长受到抑制，异种移植小鼠模型中的肿瘤生长也受到抑制。机制研究表明，沉默 Nek7 会导致体外和体内 cyclinB1 水平降低。总之，这项研究首次强调了 Nek7 在 HCC 进展中的可能作用。 Nek7 将是一种有用的生物标志物，可以早期预测 HCC 患者预后不良的风险较高。此外，Nek7 可能成为一种新的 HCC 治疗靶点。
NIMA-related kinase-7 (Nek7) is a serine/threonine kinase involved in cell-cycle progression via mitotic spindle formation and cytokinesis. In this study, we investigated whether Nek7 involves in hepatocellular carcinoma (HCC). Interestingly, we found that Nek7 was significantly overexpressed in HCC than in liver tissues. In HCC patients, high Nek7 expression was significantly correlated with tumor numbers, tumor diameter, adjacent organs invasion, tumor grade and TNM stage. Furthermore, Nek7 expression pattern showed close relationship with that of Ki-67, a well-stablished cell proliferation marker. More importantly, patients with higher expression levels of Nek7 had significantly lower 5-years survival rate. Likewise, Nek7 expression was significantly higher in HCC cell lines than normal hepatic cell line. By Nek7 silencing using lentivirus-mediated Nek7 interference approach, the growth of HCC cell lines was inhibited and the tumor growth in xenograft mouse model was also suppressed. Mechanistic studies showed that silencing of Nek7 resulted in decreasing cyclinB1 level both in vitro and in vivo. In conclusion, this study highlights for the first time the possible role of Nek7 in HCC progression. Nek7 would be a useful biomarker that early predicts HCC patients at higher risk of poor prognosis. Also, Nek7 could be a novel HCC therapeutic target.