Anti-Fibrotic MicroRNA-Based Intervention in Oral Submucous Fibrosis: A Scoping Review.

Background: Conventional therapies for oral submucous fibrosis (OSF) are largely conservative and have limited ability to modify the underlying fibrotic process or prevent disease progression. This limitation highlights the need for targeted molecular therapies. MicroRNAs (miRNAs) have recently emerged as promising anti-fibrotic regulators capable of modulating key profibrotic signalling pathways. Objective: To systematically map and synthesise available evidence on antifibrotic miRNA-based therapeutic interventions in OSF, including their mechanisms of action, delivery strategies, molecular targets and treatment outcomes. Methods: This scoping review followed the PRISMA-ScR guidelines and employed the Arksey and O'Malley framework. A comprehensive search was performed in various databases such as PubMed, Scopus, Web of Science, Embase, Cochrane Library and Google Scholar to collect pertinent data. Studies considered eligible comprised of experimental, in vitro, in vivo, and quasi-experimental research assessing anti-fibrotic miRNAs in OSF models. Results: Of the 329 records identified, 10 studies fulfilled the inclusion criteria. Most employed in vitro fibrotic oral fibroblast models, with two incorporating in vivo animal models. Several miRNAs with antifibrotic properties were identified, including miR-29b, miR-760-3p, miR-145 inhibitor, miR-424 inhibitor, miR-503, miR-30b-5p, miR-181a-5p, miR-29c, miR-375 and miR-204, which attenuate fibrotic responses by targeting genes and signalling pathways involved in fibrosis, including TGF-β/Smad, RAS/RAF/MEK/ERK, and epithelial-mesenchymal transition (EMT). Conclusion: Anti-fibrotic miRNA-based interventions demonstrate promising antifibrotic activity in preclinical models of OSF by modulating the profibrotic pathways and reducing fibrosis. Advanced delivery platforms have helped to overcome challenges associated with miRNA delivery; however, evidence remains largely limited to in vitro and in vivo studies and does not establish reversal of established fibrosis or clinical efficacy in patients. Future research should prioritise standardisation of experimental models and well-designed clinical trials for better understanding of therapeutic relevance and translational potential of miRNA in OSF.