Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non-small cell lung cancer cells via p53-p21 signaling pathway

J Clin Lab Anal. 2022 May;36(5):e24396. doi: 10.1002/jcla.24396. Epub 2022 Apr 4.

Abstract

Backgrounds: As a regulator of cell cycle, cell division cycle-associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported.

Methods: In our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan-Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD-1, PD-L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53-p21 pathway and regulates the cell cycle.

Result: CDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase.

Conslusion: In conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53-p21 signaling pathway, participating in the development and progression of NSCLC patients.

Keywords: CDCA5; G1 phase arrest; apoptosis; bioinformatics analyses; non-small cell lung cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Cycle / genetics
  • Cell Cycle Proteins* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • G1 Phase
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Oncogenes
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CDCA5 protein, human
  • Cell Cycle Proteins
  • Tumor Suppressor Protein p53