E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity

Article type: Research Article

Authors: Lu, Yongbin^{a; b; c; 1} | Su, Fei^{d; 1} | Yang, Hui^{e; 1} | Xiao, Yi^f | Zhang, Xiaobin^f | Su, Hongxin^g | Zhang, Tao^{d; *} | Bai, Yana^{b; h; *} | Ling, Xiaoling^{d; *}

Affiliations: [a] Scientific Development and Planing Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [b] College of Earth and Environmental Sciences, Lanzhou University, Lanzhou, Gansu, China | [c] Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [d] Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [e] International Medical Department Area B, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, Gansu, China | [f] Breast surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [g] Department of Radiotherapy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [h] School of Public Health, Lanzhou University, Lanzhou, Gansu, China

Correspondence: [*] Corresponding author: Xioaling Ling, Department of Oncology, The First of Hospital of Lanzhou University, Lanzhou, Gansu 730000, China. Tel./Fax: +86 0931 8356 661, E-mail: ldyy_lingxl@ lzu.edu.cn; Tao Zhang, Department of Oncology, The First of Hospital of %****␣cbm-33-cbm210149_temp.tex␣Line␣100␣**** Lanzhou University, Lanzhou, Gansu 730000, China. Tel./Fax: +86 0931 835 6661, E-mail: [email protected]; Yana Bai, Epidemiology and health statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China. Tel./Fax: +86 0931 891 5206, E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. The cell cycle regulator cyclin A2 (CCNA2) plays a role in tumor development. Herein, we explored the role of CCNA2 in TNBC. METHODS: We analyzed CCNA2 expression in 15 pairs of TNBC and adjacent tissues and assessed the relationship between CCNA2 expression using the tissue microarray cohort. Furthermore, we used two TNBC cohort datasets to analyze the correlation between CCNA2 and E2F transcription factor 1 (E2F1) and a luciferase reporter to explore their association. Through rescue experiments, we analyzed the effects of E2F1 knockdown on CCNA2 expression and cellular behavior. RESULTS: We found that CCNA2 expression in TNBC was significantly higher than that in adjacent tissues with similar observations in MDA-MB-231 and MDA-MB-468 cells. E2F1 was highly correlated with CCNA2 as observed through bioinformatics analysis (R= 0.80, P< 0.001) and through TNBC tissue verification analysis (R= 0.53, P< 0.001). We determined that E2F1 binds the +677 position within the CCNA2 promoter. Moreover, CCNA2 overexpression increased cell proliferation, invasion, and migration owing to E2F1 upregulation in TNBC. CONCLUSION: Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.

Keywords: TNBC, E2F1, CCNA2, tumorigenicity

DOI: 10.3233/CBM-210149

Journal: Cancer Biomarkers, vol. 33, no. 1, pp. 57-70, 2022