CDCA3 mediates p21-dependent proliferation by regulating E2F1 expression in colorectal cancer

Qian,Wenwei; Zhang,Zhiyuan; Peng,Wen; Li,Jie; Gu,Qiou; Ji,Dongjian; Wang,Qingyuan; Zhang,Yue; Ji,Bing; Wang,Sen; Zhang,Dongsheng; Sun,Yueming

doi:10.3892/ijo.2018.4538

CDCA3 mediates p21-dependent proliferation by regulating E2F1 expression in colorectal cancer

Authors:
- Wenwei Qian
- Zhiyuan Zhang
- Wen Peng
- Jie Li
- Qiou Gu
- Dongjian Ji
- Qingyuan Wang
- Yue Zhang
- Bing Ji
- Sen Wang
- Dongsheng Zhang
- Yueming Sun
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Affiliations: The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: August 23, 2018 https://doi.org/10.3892/ijo.2018.4538
Pages: 2021-2033
Copyright: © Qian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dysregulated cell cycle progression serves a crucial role in tumor development. Cell division cycle-associated 3 (CDCA3) is considered a trigger of mitotic entry; it is an important part of the S phase kinase-associated protein 1/Cullin/F-box ubiquitin ligase complex and mediates the destruction of mitosis-inhibitory kinase wee1. However, little is known about the role of CDCA3 in cancer, particularly colorectal cancer (CRC). The present study aimed to explore the biological and clinical significance of CDCA3 in CRC growth and progression. CDCA3 expression was significantly associated with tumor progression and poor survival. Overexpression of CDCA3 increased proliferation in LoVo CRC cells, whereas CDCA3 knockdown in SW480 CRC cells led to decreased proliferation, in vitro and in vivo. Further mechanistic investigations demonstrated that reduced CDCA3 expression resulted in G1/S phase transition arrest, which was attributed to a significant accumulation of p21 in SW480 cells; conversely, increased CDCA3 expression promoted G1/S phase transition through decreased p21 accumulation in LoVo cells. It was also demonstrated that CDCA3 was able to regulate the expression of transcription factor E2F1, thereby repressing p21 expression. Taken together, these results suggested that overexpression of CDCA3 may serve a crucial role in tumor malignant potential and that CDCA3 may be used as a prognostic factor and a potential therapeutic target in CRC.

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