2. Academic Validation
  3. circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast-myofibroblast transition

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

  • J Oral Pathol Med. 2024 May 27. doi: 10.1111/jop.13559.
Xin Bin 1,  Jing-Yi Cheng 2,  Zhi-Yuan Deng 1 3,  Bo Li 2,  Xing-Huan-Yu Xu 2,  Ou-Sheng Liu 3 4,  Zhangui Tang 1 3
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital of Central South University, Central South University, Changsha, China.
  • 2 Xiangya School of Stomatology, Central South University, Changsha, China.
  • 3 Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, China.
  • 4 Department of Orthodontics, Xiangya Stomatological Hospital of Central South University, Central South University, Changsha, China.
PMID: 38802299 DOI: 10.1111/jop.13559
Abstract

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.

Keywords

FAK/PI3K/AKT pathway; circMTO1; fibroblast–myofibroblast transition; miR‐30c‐5p; oral submucous fibrosis.

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