E2F8 regulates the proliferation and invasion through epithelial-mesenchymal transition in cervical cancer

Int J Biol Sci. 2020 Jan 1;16(2):320-329. doi: 10.7150/ijbs.37686. eCollection 2020.

Abstract

The transcription factor E2F is an important modulator of the cell cycle, and the unrestricted activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. E2F8 is known to play an important role in embryonic development and cell cycle control by inhibiting E2F1. However, it is not yet known whether E2F8 is involved in the progression of cervical cancer. In this study, the functional consequences of E2F8 knockdown in vitro and in vivo were explored. To demonstrate the function of E2F8 in cell proliferation, migration and invasion, we knocked down E2F8 in cervical cancer cell lines; in vitro and in vivo experiments using this knockdown showed that E2F8 potently induced the expression of epithelial-mesenchymal transition (EMT) markers. Finally, clinical data confirmed that E2F8 was a significant predictive factor for progression-free survival, and that patients with cervical cancer who exhibited high expression of E2F8 showed high FIGO stages and frequent recurrence rates compared to patients with low E2F8 expression. In conclusion, our study suggests that E2F8 is highly correlated with the progression-free survival of cervical cancer patients.

Keywords: E2F8; cervical cancer; epithelial-mesenchymal transition; invasion; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Wound Healing

Substances

  • E2F8 protein, human
  • Repressor Proteins