Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas
Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas
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DOI：
10.7314/apjcp.2014.15.20.8623
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Peng, Yu-Ping
中科院分区：
文献类型：
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作者：
Liu, Qiang;Dai, She-Jiao;Peng, Yu-Ping
背景：作为NDC80着丝点复合体的重要组成部分，NUF2对着丝点-微管附着和染色体分离至关重要。以往的研究也提示其参与多种人类癌症的发生发展，但其在人肝细胞癌（HCC）中的表达和功能尚不清楚。材料和方法：在本研究中，我们旨在验证NUF2在人类hcc中异常并与细胞生长相关的假设。结果：我们的研究结果显示，与邻近正常组织相比，人肝癌组织中NUF2的表达明显升高，并且在HCC细胞系中有高表达。在HepG2人肝癌细胞中使用慢病毒介导的NUF2沉默，我们发现NUF2的缺失明显抑制了体外增殖和集落形成能力，并显著阻碍了体内异种移植物的肿瘤生长。此外，NUF2沉默可诱导细胞周期阻滞，引发细胞凋亡。此外，还观察到细胞周期蛋白B1、Cdc25A、Cdc2、Bad和Bax等细胞周期和凋亡相关蛋白水平的改变。结论：综上所述，这些结果表明NUF2在HCC细胞增殖和凋亡的调控中起着至关重要的作用，表明NUF2可能作为潜在的治疗靶点。
Background: As an important component of the NDC80 kinetochore complex, NUF2 is essential for kinetochore-microtubule attachment and chromosome segregation. Previous studies also suggested its involvement in development of various kinds of human cancers, however, its expression and functions in human hepatocellular carcinoma (HCC) are still unclear. Materials and Methods: In the present study, we aimed to test the hypothesis that NUF2 is aberrant in human HCCs and associated with cell growth. Results: Our results showed significantly elevated expression of NUF2 in human HCC tissues compared to adjacent normal tissues, and high expression of NUF2 in HCC cell lines. Using lentivirus-mediated silencing of NUF2 in HepG2 human HCC cells, we found that NUF2 depletion markedly suppressed proliferation and colony formation capacity in vitro, and dramatically hampered tumor growth of xenografts in vivo. Moreover, NUF2 silencing could induce cell cycle arrest and trigger cell apoptosis. Additionally, altered levels of cell cycle and apoptosis related proteins including cyclin B1, Cdc25A, Cdc2, Bad and Bax were also observed. Conclusions: In conclusion, these results demonstrate that NUF2 plays a critical role in the regulation of HCC cell proliferation and apoptosis, indicating that NUF2 may serve as a potential molecular target for therapeutic approaches.