Post-translational modifications in the oral microenvironment: Stem cell regulation from periodontal regeneration to oral cancer therapy

Table 2 Post-translational modification signatures in malignancy-associated dental stem-cell populations

Stem-cell type	Tissue source	Dominant PTMs reported	Key regulatory enzymes	Regenerative potency/tumorigenic capacity	Ref.
OCSCs (CD44+/ALDH1+)	Primary OSCC tumour tissues & spheres	m6A RNA methylation; H3K27 trimethylation; K63/K48-linked ubiquitination; STAT3 Tyr705 phosphorylation	METTL3; EZH2; Skp2; STAT3	High tumour-initiation, chemoresistance, EMT plasticity	[59,76,82-84]
Inflammation-transformed PDLSCs	Chronic periodontitis-affected periodontal ligament	H3K27 trimethylation; H3K9 acetylation imbalance; Smurf1-mediated ubiquitination	EZH2; GCN5; Smurf1	Diminished osteogenic potential; pro-malignant phenotypes	[27,36,41,105]

PTM: Post-translational modification; OCSCs: Oral cancer stem cells; ALDH: Aldehyde dehydrogenase; PDLSCs: Periodontal ligament stem cells; OSCC: Oral squamous cell carcinoma; K63/K48: Lysine-63/-48-linked polyubiquitin; STAT3: Signal transducer and activator of transcription 3; METTL3: Methyltransferase-like 3; EZH2: Enhancer of zeste homolog 2; Skp2: S-phase kinase-associated protein 2; GCN5: General control non-depressible 5; EMT: Epithelial-mesenchymal transition.