CDCA7 Facilitates Tumor Progression by Directly Regulating CCNA2 Expression in Esophageal Squamous Cell Carcinoma

Hongyi Li; Yongjia Weng; Shaojie Wang; Fang Wang; Yanqiang Wang; Pengzhou Kong; Ling Zhang; Caixia Cheng; Heyang Cui; Enwei Xu; Shuqing Wei; Dinghe Guo; Fei Chen; Yanghui Bi; Yongsheng Meng; Xiaolong Cheng; Yongping Cui

doi:10.3389/fonc.2021.734655

CDCA7 Facilitates Tumor Progression by Directly Regulating CCNA2 Expression in Esophageal Squamous Cell Carcinoma

Front Oncol. 2021 Oct 19:11:734655. doi: 10.3389/fonc.2021.734655. eCollection 2021.

Authors

Hongyi Li^{1

2}, Yongjia Weng^{1

2}, Shaojie Wang^{1

2}, Fang Wang^{1

2}, Yanqiang Wang^{1

2}, Pengzhou Kong^{1

2}, Ling Zhang^{1

2}, Caixia Cheng³, Heyang Cui^{1

2}, Enwei Xu⁴, Shuqing Wei⁵, Dinghe Guo^{1

2}, Fei Chen^{1

2}, Yanghui Bi⁶, Yongsheng Meng⁷, Xiaolong Cheng^{1

2}, Yongping Cui^{1

2}

Affiliations

¹ Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, China.
² Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.
³ Department of Pathology, the First Hospital, Shanxi Medical University, Taiyuan, China.
⁴ Department of Pathology, Shanxi Province Cancer Hospital, Taiyuan, China.
⁵ Department of Thoracic Surgery (Ⅰ), Shanxi Province Cancer Hospital, Taiyuan, China.
⁶ The Science Research Center, Shanxi Bethone Hospital, Taiyuan, China.
⁷ Tumor Biobank, Shanxi Province Cancer Hospital, Taiyuan, China.

Abstract

Background: CDCA7 is a copy number amplified gene identified not only in esophageal squamous cell carcinoma (ESCC) but also in various cancer types. Its clinical relevance and underlying mechanisms in ESCC have remained unknown.

Methods: Tissue microarray data was used to analyze its expression in 179 ESCC samples. The effects of CDCA7 on proliferation, colony formation, and cell cycle were tested in ESCC cells. Real-time PCR and Western blot were used to detect the expression of its target genes. Correlation of CDCA7 with its target genes in ESCC and various SCC types was analyzed using GSE53625 and TCGA data. The mechanism of CDCA7 was studied by chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay.

Results: The overexpression of CDCA7 promoted proliferation, colony formation, and cell cycle in ESCC cells. CDCA7 affected the expression of cyclins in different cell phases. GSE53625 and TCGA data showed CCNA2 expression was positively correlated with CDCA7. The knockdown of CCNA2 reversed the malignant phenotype induced by CDCA7 overexpression. Furthermore, CDCA7 was found to directly bind to CCNA2, thus promoting its expression.

Conclusions: Our results reveal a novel mechanism of CDCA7 that it may act as an oncogene by directly upregulating CCNA2 to facilitate tumor progression in ESCC.

Keywords: CCNA2; CDCA7; ESCC (esophageal squamous cell carcinoma); cell cycle; copy number amplification.