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

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.734655

DOI=10.3389/fonc.2021.734655

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p><italic>CDCA7</italic> 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.</p></sec><sec><title>Methods</title><p>Tissue microarray data was used to analyze its expression in 179 ESCC samples. The effects of <italic>CDCA7</italic> 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 <italic>CDCA7</italic> with its target genes in ESCC and various SCC types was analyzed using GSE53625 and TCGA data. The mechanism of <italic>CDCA7</italic> was studied by chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay.</p></sec><sec><title>Results</title><p>The overexpression of <italic>CDCA7</italic> promoted proliferation, colony formation, and cell cycle in ESCC cells. <italic>CDCA7</italic> affected the expression of cyclins in different cell phases. GSE53625 and TCGA data showed <italic>CCNA2</italic> expression was positively correlated with <italic>CDCA7</italic>. The knockdown of <italic>CCNA2</italic> reversed the malignant phenotype induced by <italic>CDCA7</italic> overexpression. Furthermore, <italic>CDCA7</italic> was found to directly bind to <italic>CCNA2</italic>, thus promoting its expression.</p></sec><sec><title>Conclusions</title><p>Our results reveal a novel mechanism of <italic>CDCA7</italic> that it may act as an oncogene by directly upregulating <italic>CCNA2</italic> to facilitate tumor progression in ESCC.</p></sec>