RGD Reference Report - siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis. - Rat Genome Database

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

Authors: Kaneko, Naoyuki  Miura, Koh  Gu, Zhaodi  Karasawa, Hideaki  Ohnuma, Shinobu  Sasaki, Hiroyuki  Tsukamoto, Nobukazu  Yokoyama, Satoru  Yamamura, Akihiro  Nagase, Hiroki  Shibata, Chikashi  Sasaki, Iwao  Horii, Akira 
Citation: Kaneko N, etal., Biochem Biophys Res Commun. 2009 Dec 25;390(4):1235-40. doi: 10.1016/j.bbrc.2009.10.127. Epub 2009 Oct 28.
RGD ID: 28867241
Pubmed: PMID:19878654   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2009.10.127   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NDC80Humancolorectal cancer  IEP mRNA:increased expression:colorectumRGD 
NUF2Humancolorectal cancer  IEP mRNA:increased expression:colorectumRGD 
Ndc80Mousecolorectal cancer  ISONDC80 (Homo sapiens)mRNA:increased expression:colorectumRGD 
Ndc80Ratcolorectal cancer  ISONDC80 (Homo sapiens)mRNA:increased expression:colorectumRGD 
Nuf2Ratcolorectal cancer  ISONUF2 (Homo sapiens)mRNA:increased expression:colorectumRGD 
Nuf2Mousecolorectal cancer  ISONUF2 (Homo sapiens)mRNA:increased expression:colorectumRGD 
NDC80Humanstomach cancer  IEP mRNA:increased expression:stomachRGD 
NUF2Humanstomach cancer  IEP mRNA:increased expression:stomachRGD 
Ndc80Ratstomach cancer  ISONDC80 (Homo sapiens)mRNA:increased expression:stomachRGD 
Ndc80Mousestomach cancer  ISONDC80 (Homo sapiens)mRNA:increased expression:stomachRGD 
Nuf2Ratstomach cancer  ISONUF2 (Homo sapiens)mRNA:increased expression:stomachRGD 
Nuf2Mousestomach cancer  ISONUF2 (Homo sapiens)mRNA:increased expression:stomachRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ndc80  (NDC80 kinetochore complex component)
Nuf2  (NUF2 component of NDC80 kinetochore complex)

Genes (Mus musculus)
Ndc80  (NDC80 kinetochore complex component)
Nuf2  (NUF2, NDC80 kinetochore complex component)

Genes (Homo sapiens)
NDC80  (NDC80 kinetochore complex component)
NUF2  (NUF2 component of NDC80 kinetochore complex)


Additional Information