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Updated: Jun 25, 2025
Author Spotlight: Unlocking the Mysteries of Oral Potential Malignancies
Published on: August 11, 2023
circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast-myofibroblast
Xin Bin1, Jing-Yi Cheng2, Zhi-Yuan Deng1,3
1Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital of Central South University, Central South University, Changsha, China.
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.
Insights
Circular RNA mitochondrial translation optimization 1 homologue (circMTO1) is decreased in oral submucous fibrosis (OSF). CircMTO1 suppresses fibroblast-myofibroblast transition by regulating the miR-30c-5p/SOCS3 axis and FAK/PI3K/AKT pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Oral submucous fibrosis (OSF) is a potentially malignant disorder with an unclear molecular basis.
- Circular RNAs (circRNAs) are implicated in various diseases, but their role in OSF is largely unknown.
- This study investigates the expression and function of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF.
Purpose of the Study:
- To determine the expression levels of circMTO1 in OSF tissues and cells.
- To elucidate the role of circMTO1 in regulating fibroblast-myofibroblast transition (FMT) in OSF.
- To uncover the molecular mechanism by which circMTO1 exerts its effects in OSF.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blotting to detect molecule expression.
- Wound healing and Transwell assays to assess fibroblast migration and invasion.
- Dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays to investigate molecular interactions.
- Fluorescence in situ hybridization (FISH) for colocalization studies.
Main Results:
- circMTO1 and SOCS3 expression were decreased, while miR-30c-5p expression was increased in OSF patients and arecoline-stimulated buccal mucosal fibroblasts (BMFs).
- Overexpression of circMTO1 inhibited FMT, reduced BMF migration and invasion, and increased Coll I, α-SMA, and Vimentin expression.
- circMTO1 suppressed FMT by enhancing SOCS3 expression via sponging miR-30c-5p, thereby inactivating the FAK/PI3K/AKT pathway.
Conclusions:
- The circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs through the FAK/PI3K/AKT pathway.
- circMTO1 plays a protective role in OSF by inhibiting FMT.
- Further validation in larger cohorts and in vivo studies are warranted to explore circMTO1 as a potential therapeutic target for OSF.
