Proteomic identification of cyclophilin A as a potential biomarker and therapeutic target in oral submucous fibrosis

Oncotarget. 2016 Sep 13;7(37):60348-60365. doi: 10.18632/oncotarget.11254.

Abstract

Oral submucous fibrosis (OSF) is a pre-cancerous lesion, which is characterized by fibrosis of the oral submucosa. Despite large body of studies focusing on this disease, the molecular mechanisms underlying the progression of OSF remained unclear. In this study, 2-DE-based proteomic approaches were employed to identify the differently expressed proteins between OSF and normal tissues. In total, 88 proteins were identified with altered expression levels, including CypA. Upregulation of CypA was further validated through immunohistochemistry staining combined with Q-PCR and western blot by using clinical samples. Statistical analyses reveal that CypA expression level is correlated to the progression of OSF. Finally, functional study reveals a pro-proliferative property of CypA in fibroblast cells by using multiple in vitro models. The present data suggest that CypA might be a potential biomarker and therapeutic target for OSF, and will lead to a better understanding of OSF pathogenesis.

Keywords: CypA; fibroblast; oral submucous fibrosis; proteomics.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cyclophilin A / genetics
  • Cyclophilin A / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Fibroblasts / metabolism*
  • Humans
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Oral Submucous Fibrosis / metabolism*
  • Proteomics / methods*
  • RNA Interference
  • Tandem Mass Spectrometry

Substances

  • Biomarkers
  • Cyclophilin A