EIF5A2 Is Involved in the Biological Process of Cervical Cancer Cells through AGR2

Pharmacology. 2022;107(7-8):376-385. doi: 10.1159/000524017. Epub 2022 May 31.

Abstract

Introduction: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer.

Methods: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined.

Results: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells.

Conclusion: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

Keywords: Anterior gradient 2; Biological process; Cervical cancer; Eukaryotic initiation factor-5A2.

MeSH terms

  • Biological Phenomena*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Humans
  • Mucoproteins / genetics
  • Mucoproteins / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / genetics

Substances

  • AGR2 protein, human
  • Mucoproteins
  • Oncogene Proteins
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • Cisplatin