Role and mechanism of FLNa and UCP2 in the development of cervical cancer

Oncol Rep. 2020 Dec;44(6):2656-2668. doi: 10.3892/or.2020.7819. Epub 2020 Oct 21.

Abstract

Recent studies have reported that filamin A (FLNa) and uncoupling protein 2 (UCP2) are highly expressed in various types of cancer, but little is currently known about their roles in cervical cancer (CC). In the present study, immunohistochemical staining of paraffin sections of cervical tissues was performed in order to compare the differential expression of FLNa, UCP2, p16 and Ki67 between CC and high‑grade intraepithelial neoplasia (HSIL). UCP2 and FLNa were knocked down in CC cell lines to investigate the effects on cell proliferation, cell cycle arrest, apoptosis, migration and invasion. In addition, the present study investigated the expression of cell‑associated proteins [extracellular signal‑regulated kinase (ERK), phosphorylated (p) ERK, protein kinase B (AKT), p‑AKT and B‑cell lymphoma‑2 (Bcl‑2)] and the mRNA levels of cellular proteins such as Ras, matrix metalloproteinase (MMP)‑2 and MMP‑9. FLNa and UCP2 expression levels were significantly higher in CC tissues than in HSIL tissues, with no significant differential expression of p16 or Ki67. UCP2 expression was significantly different in patients with clinical stage II or higher or lymph node metastasis compared with in other patients with cervical cancer. FLNa or UCP2 knockdown slowed or decreased SiHa and HeLa cell proliferation, migration and invasion, with no significant change in apoptosis, and downregulated the protein levels of p‑ERK1/2, and the mRNA levels of Ras, MMP‑2 and MMP‑9. UCP2 knockdown arrested the cell cycle at the G2 phase in SiHa and HeLa cells, while FLNa knockdown arrested the cell cycle at the G2 phase in HeLa cells. The results of the present study revealed that FLNa and UCP2 play roles in the development and progression of CC via the Ras/MAPK/ERK signalling pathway. FLNa and UCP2 are superior to p16 and Ki67 for early prediction of CC, indicating that FLNa and UCP2 may be used for the early diagnosis of CC. UCP2 may be used to predict the prognosis of CC.

Keywords: FLNa; UCP2; cervical cancer; diagnosis; proliferation; apoptosis; migration; invasion.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cervix Uteri / pathology
  • Disease Progression
  • Female
  • Filamins / analysis
  • Filamins / genetics
  • Filamins / metabolism*
  • G2 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • MAP Kinase Signaling System
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Uncoupling Protein 2 / analysis
  • Uncoupling Protein 2 / genetics
  • Uncoupling Protein 2 / metabolism*
  • Uterine Cervical Dysplasia / pathology*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology*

Substances

  • FLNA protein, human
  • Filamins
  • UCP2 protein, human
  • Uncoupling Protein 2