siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis
siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis
复制标题
DOI：
10.1016/j.bbrc.2009.10.127
复制
发表时间：
2009-12-25
影响因子：
3.1
通讯作者：
Horii, Akira
中科院分区：
文献类型：
--
作者：
Kaneko, Naoyuki;Miura, Koh;Horii, Akira
ndc 80在有丝分裂中微管-动粒稳定附着、染色体排列和纺锤体检查点激活中起重要作用。它由两个异二聚体CDCA 1-KNTC 2和SPC 24-SPC 25组成。据报道，CDCA 1和KNTC 2的过表达与非小细胞肺癌（NSCLC）的不良预后相关，并且已经发现siRNA介导的针对CDCA 1或KNTC 2的敲低抑制NSCLC、卵巢癌、宫颈癌和胶质瘤中的细胞增殖和诱导凋亡。因此，CDCA 1和KNTC 2可以被认为是分子靶向治疗以及某些癌症诊断的良好候选者。然而，Ndc 80复合物在结直肠癌和胃癌（CRC和CC）中的作用仍不清楚。在本研究中，我们使用qRT-PCR来评估CDCA 1、KNTC 2、SPC 24和SPC 25在CRC和CC中的表达水平，并使用siRNA介导的敲低来检测细胞增殖和凋亡。与相应的正常粘膜相比，在CRC和GC中观察到这四个基因的mRNA过表达。此外，CDCA 1、KNTC 2、SPC 24和SPC 25在CRC中的表达水平与肿瘤/正常比值相关。MTT分析显示，siRNA介导的CDCA 1或KNTC 2敲低后的细胞生长受到显著抑制，流式细胞术分析显示，两种基因敲低后subG 1组分显著增加。我们目前的研究结果表明，表达控制Ndc 80的组分分子可以用于CRC和CC患者的分子靶向治疗。(C)2009 Elsevier Inc. All rights reserved.
Ndc80 has been shown to play an important role in stable microtubule-kinetochore attachment, chromosome alignment, and spindle checkpoint activation in mitosis. it is composed of two heterodimers, CDCA1-KNTC2 and SPC24-SPC25. Overexpression of CDCA1 and KNTC2 is reported to be associated with poor prognosis in non-small cell lung cancers (NSCLC), and siRNA-mediated knockdown against CDCA1 or KNTC2 has been found to inhibit cell proliferation and induction of apoptosis in NSCLC, ovarian cancer, cervical cancer and glioma. Therefore, CDCA1 and KNTC2 can be considered good candidates for molecular target therapy as well as diagnosis in some cancers. However, the role of the Ndc80 complex in colorectal and gastric cancers (CRC and CC) still remains unclear. in the present study, we used qRT-PCR to evaluate the expression levels of CDCA1, KNTC2, SPC24 and SPC25 in CRC and CC and employed siRNA-mediated knockdown to examine cell proliferation and apoptosis. mRNA overexpression of these four genes was observed in CRCs and GCs when compared with the corresponding normal mucosae. Additionally, the expression levels of tumor/normal ratios of CDCA1, KNTC2, SPC24 and SPC25 correlated with each other in CRCs. MTT assays revealed that cell growths after the siRNA-mediated knockdown of either CDCA1 or KNTC2 were significantly suppressed, and flow cytometry analyses revealed significant increases of the subG1 fractions after knockdown against both genes. Our present results suggest that expressional control of component molecules of Ndc80 can be utilized for molecular target therapy of patients with CRC and CC. (C) 2009 Elsevier Inc. All rights reserved.