J Cancer 2022; 13(7):2322-2335. doi:10.7150/jca.64747 This issue

Research Paper

CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1

Cheng Xiang1#, Wu-hui Sun1#, You Ke2, Xing Yu1, Yong Wang1✉

1. Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang, China.
2. Department of Nephrology, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang, China.
# These authors contribute equally to this work.

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Citation:
Xiang C, Sun Wh, Ke Y, Yu X, Wang Y. CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1. J Cancer 2022; 13(7):2322-2335. doi:10.7150/jca.64747. Available from https://www.jcancer.org/v13p2322.htm

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Abstract

Graphic abstract

Background: This study aims to reveal regulatory role of cell division cycle associated 8 (CDCA8) in thyroid cancer progression and metastasis.

Methods: A series of experiments in vivo and in vitro were performed to explore the function of CDCA8 in thyroid cancer.

Results: Immunohistochemical analysis showed that CDCA8 expression levels were upregulated in thyroid cancer tissues compared with normal tissues, and were statistically correlated with tumor stage. Results of in vitro loss-of-function assay showed that downregulation of endogenous expression of CDCA8 could significantly inhibit cell proliferation, colony formation, cell migration, and promote apoptosis. Thyroid cancer cells lacking CDCA8 expression also had reduced tumorigenicity in vivo. Further, results of preliminary mechanistic exploration showed that CDK1 may be a potential downstream molecule of CDCA8 in regulating thyroid cancer progression. We subsequently confirmed that CDK1 itself exerted a significant regulatory function in thyroid cancer by loss- and gain-of-function experiments. Moreover, overexpression of CDK1 could weaken the tumor suppressive effect caused by CDCA8 knockdown.

Conclusions: CDCA8 functions as an oncogene in thyroid cancer, and CDCA8 knockdown suppresses cancer development in vitro and in vivo. Additionally, CDK1 was further identified as a potential target of CDCA8 in thyroid cancer.

Keywords: thyroid cancer, CDCA8, CDK1, cell proliferation, cell apoptosis