RAD18 contributes to the migration and invasion of human cervical cancer cells via the interleukin‑1β pathway

Mol Med Rep. 2019 Oct;20(4):3415-3423. doi: 10.3892/mmr.2019.10564. Epub 2019 Aug 6.

Abstract

The E3 ubiquitin ligase RAD18 has been identified as an oncoprotein that exhibits prometastatic properties in various types of cancer; however, the role of RAD18 in cervical cancer (CC) remains unclear. In the present study, it was revealed that increased expression of RAD18 was associated with worse prognosis of patients with CC. Knockdown of endogenous RAD18 suppressed the motility and invasiveness of CC cells, as evaluated by Transwell assays. mRNA sequencing revealed that silencing RAD18 altered the expression profile of proinflammatory mediators, such as interleukin‑1β (IL‑1β). Furthermore, exogenous IL‑1β treatment rescued RAD18‑mediated CC cell invasion. These findings indicated an underlying mechanism via which RAD18 promotes CC progression, suggesting that RAD18 may be a potential biomarker and therapeutic target for malignant CC.

MeSH terms

  • Adult
  • Aged
  • Cell Movement*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Interleukin-1beta / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Signal Transduction*
  • Ubiquitin-Protein Ligases / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • DNA-Binding Proteins
  • IL1B protein, human
  • Interleukin-1beta
  • Neoplasm Proteins
  • RAD18 protein, human
  • Ubiquitin-Protein Ligases