CDT1, Transcriptionally Regulated by E2F2, Promotes Lung Adenocarcinoma Progression

Abstract

CDT1, a gene that exhibited excessive expression in various malignancies, functioned as a pivotal regulator of replication licensing. In this study, a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD) was observed. Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1 by Chip-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Moreover, we identified an upregulation of CDT1 at the RNA level in Chinese LUAD samples. Remarkably, in the loss-of-function assays the depletion of CDT1 in LUAD cell lines impeded cell proliferation, migration, and invasion, while concurrently promoting cell apoptosis and inducing G0/G1 phase arrest using a combination of MTT, flow cytometry, and Transwell assays, thus reinforcing its role as an oncogene. Furthermore, enhanced tumor ablation in a CDT1 downregulated LAUD tumor-bearing nude mouse model was determined. Collectively, our results strongly suggested that E2F2 positively regulated CDT1 expression and actively participated in the progression of lung adenocarcinoma, thereby providing valuable insights into the identification of novel therapeutic targets for the treatment of LUAD.

Note:
Funding Declaration: This work was supported by grants from the General Project of Fujian Natural Science Foundation Project (No. 2020J011129), Beijing Bethune Charitable Foundation (BJ-RW2020005J) and key disciplines and specialties at Joint Logistic Support Force level (LQYZ-HX).

Conflicts of Interest: None

Ethical Approval: The procedures for care and use of animals were approved by the Ethics Committee of the Ethics Review Committee of the 900th Hospital of the Joint Logistic Support Force, People’s Liberation Army and all applicable institutional and governmental regulations concerning the ethical use of animals were followed. This study was approved by the Ethics Review Committee of the 900th Hospital of the Joint Logistic Support Force, People’s Liberation Army (approval number:2020034). Written informed consent was provided to all patients participating in the study.

Keywords: E2F2, CDT1, lung adenocarcinoma, oncogene