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

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-beta signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-beta/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.

Automated summary

Oral submucous fibrosis (OSF) is a potentially malignant disorder characterized by inflammation and collagen deposition. This study found that miR-424 was overexpressed in OSF tissues and played a role in maintaining myofibroblast characteristics. The suppression of miR-424 reduced myofibroblast activities and downregulated fibrosis markers by binding to TGIF2 and activating the TGF-beta/Smad pathway. Targeting the miR-424/TGIF2 axis may be a promising approach for OSF treatment.