MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

Abstract

Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-β signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-β/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.

Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis

“…For example, miR-424 is aberrantly overexpressed in OSF tissues, and the suppression of miR-424 markedly reduces collagen contractility, migration ability and downregulates the expression of fibrosis markers via directly binding to TGIF2. 42 The profibrotic molecule miR-155 is involved in the pathogenesis of oxidative stress-associated OSF through the regulation of RPTOR. In addition, some miRNAs possess the function of inhibiting fibrogenesis.…”