miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis

J Formos Med Assoc. 2019 Jul;118(7):1093-1098. doi: 10.1016/j.jfma.2019.02.014. Epub 2019 Mar 28.

Abstract

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis.

Methods: The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot.

Results: MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246.

Conclusion: MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs.

Keywords: Buccal mucosal fibroblasts; MicroRNA-1246; Oral submucous fibrosis; Type I collagen.

MeSH terms

  • Cell Transdifferentiation / genetics
  • Cells, Cultured
  • Collagen Type I / metabolism
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mouth Mucosa / pathology
  • Myofibroblasts / metabolism*
  • Oral Submucous Fibrosis / genetics*
  • Oral Submucous Fibrosis / pathology*
  • Precancerous Conditions / pathology

Substances

  • Collagen Type I
  • MIRN1246 microRNA, human
  • MicroRNAs