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Published on: November 2, 2020
Therapeutic potential of targeting cell division cycle associated 5 for oral squamous cell carcinoma
Norihiko Tokuzen1, Koh-ichi Nakashiro1, Hiroshi Tanaka1
1Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
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.
Insights
Targeting cell division cycle associated 5 (CDCA5) shows promise for oral squamous cell carcinoma (OSCC) therapy. Inhibiting CDCA5 significantly reduced OSCC cell growth and invasion, suggesting it as a key therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Molecularly targeted therapies have advanced cancer treatment, but progress for oral squamous cell carcinoma (OSCC) has been slower.
- Identifying novel molecular targets is crucial for developing effective OSCC therapies.
Purpose of the Study:
- To investigate the expression and functional role of cell division cycle associated 5 (CDCA5) in oral squamous cell carcinoma (OSCC).
- To evaluate CDCA5 as a potential therapeutic target for OSCC.
Main Methods:
- Microarray analysis to identify overexpressed genes in OSCC.
- Quantitative RT-PCR and Western blotting to confirm CDCA5 expression in OSCC cell lines.
- Small interfering RNA (siRNA) to knockdown CDCA5 expression.
- In vitro and in vivo assays to assess the effect of CDCA5 knockdown on cell growth and invasion.
- Immunohistochemical analysis of CDCA5 expression in 80 OSCC patient samples.
Main Results:
- CDCA5 was found to be overexpressed in human OSCC cell lines.
- Knockdown of CDCA5 significantly inhibited OSCC cell growth both in vitro and in vivo.
- Higher CDCA5 expression levels in patient samples were significantly associated with poorer overall survival.
Conclusions:
- CDCA5 is a critical gene that promotes the progression of oral squamous cell carcinoma (OSCC).
- Targeting CDCA5 represents a promising therapeutic strategy for the treatment of OSCC.
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