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NCAPH plays important roles in human colon cancer

机译:NCAPH在人类结肠癌中起重要作用

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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.
机译:结肠癌(CC)是全球主要的恶性肿瘤之一,其发病机理很复杂,需要多种基因和信号通路的累积改变。凝缩蛋白是多蛋白复合物,在有丝分裂,减数分裂甚至肿瘤发生过程中,在染色体装配和分离中起关键作用。使用免疫组织化学和苏木精-伊红染色的组织芯片,​​我们发现结肠癌组织中的非SMC凝集素I复合亚基H(NCAPH)高于所有相应的邻近非癌组织。然后,我们对CC中NCAPH的确切功能进行了表征。我们提供的证据表明,与正常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患者中鉴定出许多NCAPH突变。我们发现耗尽NCAPH会抑制CC细胞增殖,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,NCAPH在结肠癌患者肿瘤组织中的高表达与低表达患者的预后和生存率相比有显着提高,这表明NCAPH高表达促进了结肠癌细胞的增殖。另一方面,它也可能使这些对化学疗法或放射疗法有反应的细胞敏感。这些发现共同揭示了NCAPH在CC中的重要作用,表明NCAPH可以在将来用作新的治疗靶标。

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