Abstract
Molecularly targeted drugs are used in the treatment of a variety of malignant tumors, but this approach to developing novel therapies for oral squamous cell carcinoma (OSCC) has lagged behind the progress seen for other cancers. We have attempted to find appropriate molecular targets for OSCC and identified cell division cycle associated 5 (CDCA5) as a cancer-related gene which was overexpressed in all the human OSCC cells tested by microarray analysis. In this study, we investigated the expression and function of CDCA5 in OSCC. First, we confirmed that CDCA5 was overexpressed in 4 human OSCC cell lines by quantitative RT-PCR and Western blotting. We then tested the effect of synthetic small interfering RNAs specific for CDCA5 on the growth and invasion of human OSCC cells. Knockdown of CDCA5 markedly inhibited the growth of OSCC cells in vitro and in vivo. We also examined the expression of CDCA5 protein in 80 cases of OSCC immunohistochemically and found a significant association between CDCA5 expression levels and overall survival. These results suggest that CDCA5 functions as a critical gene supporting OSCC progression and that targeting CDCA5 may be a useful therapeutic strategy for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is estimated 263,000 new cases and 127,000 deaths in 2008 worldwide [1]
We clarified the function of cell division cycle associated 5 (CDCA5) in the proliferation and invasiveness of human OSCC cells, by transfecting them with synthetic small interfering RNA specific for CDCA5 at a concentration of 10 nM
When we examined the effect of specific for CDCA5 (siCDCA5) on the growth and invasion of human OSCC cells, we found that CDCA5 knockdown significantly inhibited cell growth by 5081% (Figure 2B) but not invasiveness, compared to an untargeted small interfering RNA (siRNA)
Summary
Oral squamous cell carcinoma (OSCC) is estimated 263,000 new cases and 127,000 deaths in 2008 worldwide [1]. Overexpression and constitutive activation of some of these oncogenes support the proliferation, invasion, and metastasis of cancer cells. Targeting oncogenes in this way has provided novel therapeutic opportunities, the development of molecular targeted therapy for OSCC has lagged behind other cancers. We used microarray analysis and Ingenuity Pathway Analysis (IPA) to identify 465 cancer-related genes that were overexpressed in all the human OSCC cell lines examined [6]. Among these genes, we identified cell www.impactjournals.com/oncotarget
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