Arecoline enhances miR-21 to promote buccal mucosal fibroblasts activation

Background/purpose: Oral submucous fibrosis (OSF) is an irreversible fibrosis disease and a potentially malignant disorder in the oral cavity. Various studies have shown that miR-21 was implicated in the fibrogenesis and carcinogenesis, but its functional role in the development of OSF has not been investigated. Methods: The expression levels of miR-21 in arecoline-stimulated normal buccal mucosal fibroblasts (BMFs) and OSF specimens were determined by qRT-PCR. Exogenous administration of TGF-beta and its inhibitor (SB431542) were utilized to examine the involvement of TGF-beta signaling in miR-21 alteration. Collagen gel contraction, transwell migration, and invasion assays were used to assess the myofibroblast activities. The relationship between alpha-SMA and miR-21 was calculated using the Pearson correlation coefficient. Results: MiR-21 expression was induced in BMFs by arecoline treatment in a dose-dependent manner. Our results showed that this upregulation was mediated by TGF-beta signaling. Subsequently, we demonstrated that the administration of the miR-21 inhibitor suppressed the arecoline-induced myofibroblast characteristics, including a higher collagen gel contractility and cell motility, in normal BMFs. Furthermore, inhibition of miR-21 was sufficient to attenuate the myofibroblast features in fibrotic BMFs. Besides, we showed that the expression of miR-21 was aberrantly upregulated in the OSF tissues and there was a positive correlation between miR-21 and myofibroblast marker, alpha-SMA. Conclusion: MiR-21 overexpression in OSF may be due to the stimulation of areca nut, which was mediated by the TGF-beta pathway. Our data suggested that the repression of miR-21 was a promising direction to palliate the development and progression of OSF. Copyright (C) 2020, Formosan Medical Association. Published by Elsevier Taiwan LLC.

Automated summary

The study revealed that the expression of miR-21 in the development of OSF is induced by arecoline stimulation, possibly mediated through the TGF-beta signaling pathway. Inhibition of miR-21 can alleviate the development and progression of OSF, as well as suppress myofibroblast characteristics in normal and fibrotic BMFs.