IFITM3 knockdown reduces the expression of CCND1 and CDK4 and suppresses the growth of oral squamous cell carcinoma cells

Cell Oncol (Dordr). 2019 Aug;42(4):477-490. doi: 10.1007/s13402-019-00437-z. Epub 2019 Apr 4.


Purpose: Oral squamous cell carcinoma (OSCC) is a challenging disease to treat. Up to 50% of OSCC patients with advanced disease develop recurrences. Elucidation of key molecular mechanisms underlying OSCC development may provide opportunities to target specific genes and, thus, to improve patient survival. In this study, we examined the expression and functional role of interferon transmembrane protein 3 (IFITM3) in OSCC development.

Methods: The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting.

Results: We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies.

Conclusions: From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.

Keywords: CCND1; CDK4; IFITM3; Oral squamous cell carcinoma; Proliferation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Cellular Senescence
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Female
  • Gene Knockdown Techniques*
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Phosphorylation
  • RNA-Binding Proteins / metabolism*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction


  • CCND1 protein, human
  • IFITM3 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • Retinoblastoma Protein
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4