NCAPH plays important roles in human colon cancer.

NCAPH plays important roles in human colon cancer.
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NCAPH 在人类结肠癌中发挥重要作用

DOI:
10.1038/cddis.2017.88
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发表时间:
2017-03-16
影响因子:
9
通讯作者:
Chen YB
Chen YB
中科院分区:
生物学1区
文献类型:
--
作者:
Yin L;Jiang LP;Shen QS;Xiong QX;Zhuo X;Zhang LL;Yu HJ;Guo X;Luo Y;Dong J;Kong QP;Yang CP;Chen YB

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结肠癌(Colon cancer, CC)是世界范围内主要的恶性肿瘤之一,其发病机制复杂,需要多种基因和信号通路的累积改变。凝缩蛋白是一种多蛋白复合物,在有丝分裂、减数分裂甚至肿瘤发生过程中对染色体的组装和分离起着关键作用。利用组织微阵列免疫组化和苏木精-伊红染色,我们发现结肠癌组织中非smc凝血素I复合体亚单位H (NCAPH)高于所有相应的邻近非癌组织。随后,我们对NCAPH在CC中的确切功能进行了表征,我们提供的证据表明,与正常的人结肠上皮细胞相比,NCAPH在结直肠癌细胞系中高表达,并在CC患者中发现了许多NCAPH突变。我们发现NCAPH的缺失抑制CC细胞的增殖、体外迁移和体内异种移植肿瘤的形成。此外,NCAPH敲低促进细胞凋亡和细胞周期阻滞在G2/M期。有趣的是,结肠癌患者肿瘤组织中NCAPH高表达患者的预后和生存率明显优于低表达患者,提示NCAPH高表达促进结肠癌细胞增殖;另一方面,它也可能使这些细胞对化学或放射疗法产生反应。总的来说,这些发现揭示了NCAPH在CC中的重要作用,表明NCAPH可以作为未来新的治疗靶点。
Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin–eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo-or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.
DOI: 10.4161/cc.28568
发表时间: 2014
期刊: Cell cycle (Georgetown, Tex.)
影响因子: --
作者:
Tanno Y;Watanabe Y
通讯作者: Watanabe Y