Academic Journal
Knockdown of METTL3 ameliorated myofibroblast activities in oral submucous fibrosis through upregulating DKK3.
| Τίτλος: | Knockdown of METTL3 ameliorated myofibroblast activities in oral submucous fibrosis through upregulating DKK3. |
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| Συγγραφείς: | Peng J; Department of General Dentistry, Xindaxin Branch, Changsha Stomatological Hospital, Changsha, Hunan 410000, China. Electronic address: pengjing20100@163.com., Guo S; Dental Aesthetics Department, Changsha Stomatological Hospital, Changsha, Hunan 410000, China. Electronic address: guosheng11170@163.com., Zhang P; Department of General Dentistry, Xindaxin Branch, Changsha Stomatological Hospital, Changsha, Hunan 410000, China. Electronic address: zhangpeipei11060@163.com. |
| Πηγή: | Tissue & cell [Tissue Cell] 2026 Oct; Vol. 102, pp. 103544. Date of Electronic Publication: 2026 Apr 20. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Churchill Livingstone Country of Publication: Scotland NLM ID: 0214745 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3072 (Electronic) Linking ISSN: 00408166 NLM ISO Abbreviation: Tissue Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Edinburgh : Churchill Livingstone Original Publication: Edinburgh, Oliver & Boyd. |
| Ιατρικοί όροι (MeSH): | Oral Submucous Fibrosis*/pathology , Oral Submucous Fibrosis*/genetics , Oral Submucous Fibrosis*/metabolism , Myofibroblasts*/metabolism , Myofibroblasts*/pathology , Methyltransferases*/metabolism , Methyltransferases*/genetics , Adaptor Proteins, Signal Transducing*/metabolism , Adaptor Proteins, Signal Transducing*/genetics , Intercellular Signaling Peptides and Proteins*/metabolism , Intercellular Signaling Peptides and Proteins*/genetics , Up-Regulation*/genetics , Gene Knockdown Techniques*, Cell Movement/genetics ; Humans |
| Περίληψη: | Background: Oral submucous fibrosis (OSF) is a precancerous disorder characterized by abnormal buccal mucosal fibroblast (BMF)-to-myofibroblast transition. Dickkopf-related protein 3 (DKK3) is implicated in fibrosis, but its role and regulatory mechanisms in OSF remain unclear. Methods: Clinical OSF and normal tissues were analyzed for DKK3 and m6A regulator expression. Arecoline-treated BMFs were used to model OSF in vitro. The mRNA and protein expressions were analyzed by RT-qPCR, Western blot, immunofluorescence staining, and immunohistochemistry. Cell viability, migration, and invasion were detected using CCK-8 assay, wound healing assay, and transwell assay, respectively. Dot blot assay was employed to detect global m6A levels. The interaction between METTL3/YTHDF2 and DKK3 was analyzed by RIP assay. The m6A modification on DKK3 mRNA was analyzed by Me-RIP assay. Results: DKK3 was downregulated in OSF tissues and arecoline-stimulated BMFs. DKK3 overexpression inhibited arecoline-induced BMF-to-myofibroblast transition. METTL3-mediated m6A modification silenced DKK3 by recruiting YTHDF2, which degraded DKK3 mRNA. As expected, METTL3 knockdown rescued DKK3 expression and inhibited myofibroblast activities, while this effect was reversed by DKK3 co-silencing. Conclusion: The METTL3-m6A-YTHDF2 axis drove OSF progression by promoting BMF-to-myofibroblast transition through suppressing DKK3. Our study provides a research foundation for developing novel therapeutic strategies targeting OSF. (Copyright © 2026 Elsevier Ltd. All rights reserved.) |
| Contributed Indexing: | Keywords: DKK3; METTL3; Oral submucous fibrosis; YTHDF2; m6A; myofibroblast activities |
| Substance Nomenclature: | 0 (DKK3 protein, human) EC 2.1.1.- (Methyltransferases) 0 (Adaptor Proteins, Signal Transducing) EC 2.1.1.62 (METTL3 protein, human) 0 (Intercellular Signaling Peptides and Proteins) |
| Entry Date(s): | Date Created: 20260425 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.tice.2026.103544 |
| PMID: | 42033900 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-3072 |
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| DOI: | 10.1016/j.tice.2026.103544 |