Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer
Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer
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DOI：
10.1136/gut.2008.149468
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发表时间：
2009-02-01
期刊：
影响因子：
24.5
通讯作者：
Sugimura, H.
中科院分区：
文献类型：
--
作者：
Iwaizumi, M.;Shinmura, K.;Sugimura, H.
背景和目标：染色体不稳定性（CIN）被认为是癌症的标志，并且是由有丝分裂期间的纺锤体组装检查点障碍或染色体错误分离引起的。虽然最近鉴定的人shugoshin（hSgo 1），在适当的染色体分离的重要球员，已经表明hSgo 1在结直肠肿瘤发生的参与，很少有人知道它是如何参与。本研究的目的是获得有关hSgo 1在人类结直肠cancer.Method和结果的状态的信息：在46例结直肠癌病例中，hSgo 1 mRNA的表达在肿瘤组织中与相应的正常组织相比降低（p = 0.032）。人Sgo 1下调的肿瘤（肿瘤与正常粘膜的比率< 0.5）优先位于左侧大肠而不是右侧（p = 0.012），荧光原位杂交（FISH）显示着丝粒数目的变化更大。为了评估hSgo 1下调的影响，通过用短发夹RNA表达载体转染二倍体HCT 116细胞系来进行hSgo 1敲低。hSgo 1基因敲除的细胞由于G（2）/M阻滞和凋亡而增殖缓慢（p < 0.001），并且随后在hSgo 1基因敲除的细胞中观察到以非整倍体（p < 0.001）和微核（p < 0.005）形式的CIN标志物。结论：hSgo 1基因表达下调的大肠癌细胞具有CIN的临床病理特征，hSgo 1基因表达下调导致大肠癌细胞CIN的发生。
Background and aims: Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer.Method and results: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio < 0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G(2)/M arrest and apoptosis (p < 0.001), and markers of CIN in the form of aneuploidy (p < 0.001) and micronuclei (p < 0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p < 0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells.Conclusions: These findings suggest that hSgo1-down-regulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.