m6A Regulator METTL16: Breakthrough Target in Diabetic Foot Ulcer Pathogenesis
Summary: Multi-omics (bulk RNA-seq, scRNA-seq, machine learning) across datasets identified 13 DE-MRGs in DFU; METTL16, NSUN3, IGF2BP2 as top biomarkers (AUC 0.93). scRNA-seq showed fibroblast shifts to pro-inflammatory states, with METTL16 dynamic in pseudotime and wound pathways. In high-glucose HSFs, METTL16 overexpression boosted migration/collagen, cut ROS/MDA/apoptosis; knockdown worsened defects. Immune: ↑M1 macrophages, IL-17/MAPK; ↓glutathione metabolism. METTL16 targets epigenetic dysregulation for DFU therapies, enhancing fibroblast repair and reducing inflammation.
Key Highlights:
- Biomarkers: METTL16/NSUN3/IGF2BP2 (AUC 0.93 training, 0.85 validation).
- Fibroblasts: ↑migration/collagen, ↓ROS/apoptosis with METTL16 OE.
- Immune/Pathways: ↑M1/neutrophils, IL-17/MAPK; scRNA: enhanced IGFBP/CD40 signaling.
- Validation: qPCR/WB/CCK-8/wound assay in hyperglycemic HSFs.
- Authors: Tong Y, Li S, Shen L et al.
Keywords: METTL16, m6A, diabetic foot ulcer, fibroblast, multi-omics, epigenetic