Regulation of miRNA-146a and miRNA-150 Levels by Celecoxib in Premalignant Lesions of K14-HPV16 Mice

Anticancer Res. 2017 Jun;37(6):2913-2918. doi: 10.21873/anticanres.11644.

Abstract

Background/aim: Human papillomavirus type 16 (HPV16) induces various types of cancer in several locations. Microenvironmental microRNAs (miRNAs) such as miRNA-146a and miRNA-150 regulate cancer-associated inflammation and are involved in HPV-induced carcinogenesis. We studied the effects of celecoxib on the expression of these two miRNAs in HPV16-induced lesions.

Materials and methods: Female transgenic (HPV16+/-) and wild-type (HPV16-/-) mice were administered 75 mg/kg/day celecoxib orally (treatment groups) or placebo (control groups) for four weeks. Skin samples were classified histologically, or used for miRNA analysis by quantitative real-time PCR.

Results: HPV16+/- mice showed higher miRNA-146a and miRNA-150 expression levels compared to wild-type animals. Celecoxib further increased miRNA-150 (p<0.05) and miRNA-146a levels in treated animals. Celecoxib-treated HPV16+/- animals also showed reduced incidence of epidermal dysplasia and reduced inflammation, compared to untreated mice.

Conclusion: In this model, celecoxib may be able to regulate tumour-associated inflammation, through mechanisms involving the regulation of miRNA-146a and miRNA-150.

Keywords: HPV16; carcinogenesis; celecoxib; inflammation; miRNAs.

MeSH terms

  • Animals
  • Celecoxib / pharmacology*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Female
  • Human papillomavirus 16 / genetics*
  • Mice, Transgenic
  • MicroRNAs / metabolism*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / virology
  • Skin / metabolism
  • Skin / pathology

Substances

  • Cyclooxygenase 2 Inhibitors
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Mirn150 microRNA, mouse
  • Celecoxib