J Cancer 2021; 12(17):5173-5180. doi:10.7150/jca.53708 This issue

Research Paper

E2F4 Promotes the Proliferation of Hepatocellular Carcinoma Cells through Upregulation of CDCA3

Junye Liu1,3*, Lulu Xia1,3*, Shilei Wang2*, Xuefei Cai1, Xiaoli Wu1,3, Chunhong Zou1,3, Baoju Shan4,5✉, Miao Luo3,6✉, Deqiang Wang1,3✉

1. Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China.
2. Department of Dermatology and Cosmetology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
3. College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
4. Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child development and Critical Disorders; Children's Hospital of Chongqing Medical University, Chongqing, China.
5. Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.
6. Department of Clinical Laboratory, Yubei District People's Hospital, Chongqing, China.
*These authors contributed equally to this work.

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Citation:
Liu J, Xia L, Wang S, Cai X, Wu X, Zou C, Shan B, Luo M, Wang D. E2F4 Promotes the Proliferation of Hepatocellular Carcinoma Cells through Upregulation of CDCA3. J Cancer 2021; 12(17):5173-5180. doi:10.7150/jca.53708. Available from https://www.jcancer.org/v12p5173.htm

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Abstract

Graphic abstract

Liver cancer, the second most commonly diagnosed cancer, is associated with high mortality rates. E2F4 is a member of the E2F transcription factor family. There are limited studies on the role of E2F4 in hepatocellular carcinoma (HCC). In this study, the expression of E2F4 in HCC tissue samples and cell lines was analyzed using quantitative real-time polymerase chain reaction. E2F4 expression positively correlated with tumor size in patients with HCC. Additionally, E2F4 expression was greater in HCC cells than in normal LO2 cells. Furthermore, overexpression of E2F4 significantly enhanced the proliferation, migration, and invasion of HCC cells. The results of a luciferase assay revealed that E2F4 upregulated the expression of CDCA3 by binding to its promoter region (1863'-ACGCGCGAGAATG-1875') and consequently promoted proliferation and cell cycle progression of HCC cells. Taken together, these results demonstrated that E2F4 might play a vital role in HCC progression and could serve as a potential biomarker for the diagnosis and as a therapeutic target of HCC.

Keywords: hepatocellular carcinoma, E2F4, CDCA3, promoter