siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis

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• 作者：Naoyuki Kaneko ; Koh Miura ; Zhaodi Gu ; Hideaki Karasawa ; Shinobu Ohnuma ; Hiroyuki Sasaki ; Nobukazu Tsukamoto ; Satoru Yokoyama ; Akihiro Yamamura ; Hiroki Nagase ; Chikashi Shibata ; Iwao Sasaki ; Akira Hori
• 关键词：Apoptosis ; CDCA1 ; Colorectal cancer ; Gastric cancer ; Kinetochore ; KNTC2 ; Ndc80 ; RNAi ; SPC24 ; SPC25 ; Spindle checkpoint
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：25 December 2009
• 年：2009
• 卷：390
• 期：4
• 页码：1235-1240
• 全文大小：384 K

文摘

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 GC) 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 GC 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 GC.