circMTO1/miR‐30c‐5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast–myofibroblast transition

Background circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. Methods Target molecule expression was detected using RT‐qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR‐30c‐5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull‐down assays. The colocalisation of circMTO1 and miR‐30c‐5p was observed using fluorescence in situ hybridisation (FISH). Results circMTO1 and SOCS3 expression decreased, whereas miR‐30c‐5p expression increased in patients with OSF and arecoline‐stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast–myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α‐SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR‐30c‐5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. Conclusion circMTO1/miR‐30c‐5p/SOCS3 axis regulates FMT in arecoline‐treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.