Heliyon (Aug 2024)

CDT1, transcriptionally regulated by E2F2, promotes lung adenocarcinoma progression

  • Bao-Quan Lin,
  • Feng Chen,
  • Lei Gu,
  • Zai-Xin Wu,
  • Jia Ye,
  • Lei Zhang,
  • Bing-jing Huang,
  • Zong-yang Yu,
  • Guo-Xiang Lai,
  • Xiao-Peng Lan,
  • Hu Zhao,
  • Wei Liu

Journal volume & issue
Vol. 10, no. 16
p. e36557

Abstract

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CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.

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