Liu W, Yang YY, Shi ZJ. Post-translational modifications in the oral microenvironment: Stem cell regulation from periodontal regeneration to oral cancer therapy. World J Stem Cells 2025; 17(11): 112702 [DOI: 10.4252/wjsc.v17.i11.112702]
Corresponding Author of This Article
Zhuo-Jin Shi, DDS, School/Hospital of Stomatology, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, Zhejiang Province, China. shizhuojin@yeah.net
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Dentistry, Oral Surgery & Medicine
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Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 26, 2025 (publication date) through Nov 26, 2025
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World Journal of Stem Cells
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1948-0210
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Liu W, Yang YY, Shi ZJ. Post-translational modifications in the oral microenvironment: Stem cell regulation from periodontal regeneration to oral cancer therapy. World J Stem Cells 2025; 17(11): 112702 [DOI: 10.4252/wjsc.v17.i11.112702]
World J Stem Cells. Nov 26, 2025; 17(11): 112702 Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.112702
Post-translational modifications in the oral microenvironment: Stem cell regulation from periodontal regeneration to oral cancer therapy
Wei Liu, Yuan-Yuan Yang, Zhuo-Jin Shi
Wei Liu, Department of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Yuan-Yuan Yang, Department of Prosthodontics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Zhuo-Jin Shi, School/Hospital of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Author contributions: Liu W and Yang YY conducted literature review and drafted the manuscript; Shi ZJ conceptualized the study, provided critical revisions, and supervised the overall work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhuo-Jin Shi, DDS, School/Hospital of Stomatology, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou 310053, Zhejiang Province, China. shizhuojin@yeah.net
Received: August 4, 2025 Revised: September 16, 2025 Accepted: November 6, 2025 Published online: November 26, 2025 Processing time: 115 Days and 1 Hours
Abstract
The oral microenvironment plays a pivotal role in determining stem cell fate, driving both regeneration and pathological transformation. Emerging evidence suggests that post-translational modifications (PTMs) play a role as dynamic molecular signatures that regulate key signaling networks in dental-derived mesenchymal stem cells. These PTMs not only influence stem cell self-renewal and differentiation in periodontal tissue regeneration but also contribute to cancer stem cell plasticity and therapeutic resistance in oral squamous cell carcinoma (OSCC). At the pathway level, PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase (p38/c-Jun N-terminal kinase) → runt-related transcription factor 2 in regeneration, whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin, and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition. This review expounds on recent advances in PTM-mediated regulatory mechanisms in dental-derived mesenchymal stem cells, outlines their functional implications in inflammatory and tumor microenvironments, and discusses translational strategies-including localized, time-staged PTM modulation for regeneration and pathway-anchored combinations for OSCC-for regenerative medicine and targeted cancer therapies. Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.
Core Tip: Post-translational modifications act as dynamic molecular codes that steer dental-derived mesenchymal stem cells through a continuum from periodontal regeneration to oral squamous cell carcinoma stem-cell plasticity. This review integrates single-cell and spatial multi-omics evidence to map a sequential cascade-acetylation, crotonylation, phosphorylation, trimethylation, ubiquitination and N6-methyladenosine RNA methylation-that reprograms lineage commitment, immune evasion and therapy resistance. Identifying tractable post-translational modification enzymes (e.g., general control non-depressible 5, enhancer of zeste homolog 2, methyltransferase-like 3) clarifies actionable levers for regeneration and oncology.
