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Expression of CDCA3 Is a Prognostic Biomarker and Potential Therapeutic Target in Non-Small Cell Lung Cancer
Mark N Adams1, Joshua T Burgess1, Yaowu He2
1Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolloongabba, Australia.
Introduction:
NSCLC is the leading cause for cancer-related deaths worldwide. New therapeutic targets are needed, as development of resistance to current treatment, such as platinum-based chemotherapy, is inevitable. The purpose of this study was to determine the functional relevance and therapeutic potential of cell division cycle associated 3 protein (CDCA3) in NSCLC.
Methods:
The expression of CDCA3 in squamous and nonsquamous NSCLC was investigated by using bioinformatics, Western blot analysis of matched tumor and normal tissue, and immunohistochemistry of a tissue microarray. The function of CDCA3 in NSCLC was determined by using several in vitro assays with small interfering RNA depleting CDCA3 in a panel of three immortalized human bronchial epithelial cell (HBEC) lines and seven NSCLC cell lines.
Results:
In this study, cell division cycle associated 3 gene (CDCA3) transcripts were identified as highly increased in NSCLC versus in nonmalignant tissue, with high levels of CDCA3 being associated with poor patient prognosis. CDCA3 protein was also increased in NSCLC tissue and expression was limited to tumor cells. CDCA3 expression was similarly increased in a panel of NSCLC cell lines compared with in three HBEC lines. Although depletion of CDCA3 in the HBEC lines did not affect cellular proliferation, depletion of CDCA3 expression markedly reduced the proliferation of all NSCLC cell lines. CDCA3 depletion caused a defective G2/M-phase cell cycle progression, upregulation of p21 independent of p53, and induction of cellular senescence.
Conclusions:
Our findings highlight CDCA3 as a prognostic factor and potential novel therapeutic target in NSCLC through inhibition of tumor growth and promotion of tumor senescence.
Insights
Cell division cycle associated 3 protein (CDCA3) is elevated in non-small cell lung cancer (NSCLC), driving tumor growth and cell cycle progression. Targeting CDCA3 presents a promising therapeutic strategy for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- Acquired resistance to current therapies necessitates the identification of novel therapeutic targets.
- Cell division cycle associated 3 protein (CDCA3) is a potential target for NSCLC intervention.
Purpose of the Study:
- To investigate the functional role of CDCA3 in NSCLC.
- To evaluate the therapeutic potential of targeting CDCA3 in NSCLC.
Main Methods:
- Bioinformatics analysis, Western blot, and immunohistochemistry were used to assess CDCA3 expression in NSCLC tissues and cell lines.
- In vitro assays with small interfering RNA were employed to deplete CDCA3 in NSCLC and human bronchial epithelial cell lines.
- Cell proliferation, cell cycle progression, and senescence were analyzed following CDCA3 depletion.
Main Results:
- CDCA3 expression is significantly increased in NSCLC tissues and cell lines compared to non-malignant counterparts.
- High CDCA3 levels correlate with poor patient prognosis in NSCLC.
- CDCA3 depletion inhibited NSCLC cell proliferation, induced G2/M cell cycle arrest, and promoted cellular senescence.
Conclusions:
- CDCA3 is a significant prognostic factor in NSCLC.
- Targeting CDCA3 demonstrates therapeutic potential by inhibiting tumor growth and inducing senescence in NSCLC.
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