Cell-Cycle-related Protein Centromere Protein F Deficiency Inhibits Cervical Cancer Cell Growth by Inducing Ferroptosis Via Nrf2 Inactivation

Cell Biochem Biophys. 2024 Jun;82(2):997-1006. doi: 10.1007/s12013-024-01251-7. Epub 2024 Mar 27.

Abstract

Cervical cancer (CC) is one of the severe cancers that pose a threat to women's health and result in death. CENPF, the centromere protein F, plays a crucial role in mitosis by regulating numerous cellular processes, such as chromosome segregation during mitosis. According to bioinformatics research, CENPF serves as a master regulator that is upregulated and activated in cervical cancer. Nevertheless, the precise biological mechanism that CENPF operates in CC remains unclear. The aim of this study was to analyze the function of CENPF on cervical cancer and its mechanism. We conducted immunohistochemistry and western blot analysis to examine the expression levels of CENPF in both cervical cancer tissues and cells. To explore the hidden biological function of CENPF in cell lines derived from CC, we applied lentivirus transfection to reduce CENPF manifestation. CENPF's main role is to regulate ferroptosis which was assessed by analyzing Reactive Oxygen Species (ROS), malonaldehyde (MDA), etc. The vitro findings were further validated through a subcutaneous tumorigenic nude mouse model. Our research finding indicates that there is an apparent upregulation of CENPF in not merely tumor tissues but also cell lines in the carcinomas of the cervix. In vitro and vivo experimental investigations have demonstrated that the suppression of CENPF can impede cellular multiplication, migration, and invasion while inducing ferroptosis. The ferroptosis induced by CENPF inhibition in cervical cancer cell lines is likely mediated through the Nrf2/HO-1 pathway. The data herein come up with the opinion that CENPF may have a crucial role in influencing anti-cervical cancer effects by inducing ferroptosis via the triggering of the Nrf2/HO-1 signaling pathway.

Keywords: CENPF; Cell cycle; Cervical cancer; Ferroptosis; Nuclear factor E2-related factor 2.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone* / genetics
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Female
  • Ferroptosis*
  • HeLa Cells
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microfilament Proteins
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • centromere protein F
  • Chromosomal Proteins, Non-Histone
  • Heme Oxygenase-1
  • Malondialdehyde
  • Microfilament Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • RNA, Small Interfering