Expression of CDCA3 is a prognostic biomarker and potential therapeutic target in non–small cell lung cancer

Adams, Mark N., Burgess, Joshua T., He, Yaowu, Gately, Kathy, Snell, Cameron, Zhang, Shu-Dong, Hooper, John D., Richard, Derek J. and O'Byrne, Kenneth J. (2017) Expression of CDCA3 is a prognostic biomarker and potential therapeutic target in non–small cell lung cancer. Journal of Thoracic Oncology, 12 7: 1071-1084. doi:10.1016/j.jtho.2017.04.018


Author Adams, Mark N.
Burgess, Joshua T.
He, Yaowu
Gately, Kathy
Snell, Cameron
Zhang, Shu-Dong
Hooper, John D.
Richard, Derek J.
O'Byrne, Kenneth J.
Title Expression of CDCA3 is a prognostic biomarker and potential therapeutic target in non–small cell lung cancer
Journal name Journal of Thoracic Oncology   Check publisher's open access policy
ISSN 1556-1380
1556-0864
Publication date 2017-07-01
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.jtho.2017.04.018
Open Access Status Not yet assessed
Volume 12
Issue 7
Start page 1071
End page 1084
Total pages 14
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Subject 2730 Oncology
2740 Pulmonary and Respiratory Medicine
Abstract 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.
Formatted abstract
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.
Keyword CDCA3
Cell cycle
Non–small cell lung cancer
Prognostic biomarker
Senescence
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1091589
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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