Identification of the Potential Biomarkers Involved in the Human Oral Mucosal Wound Healing: A Bioinformatic Study

Abstract

Objective. To identify the key genetic and epigenetic mechanisms involved in the wound healing process after injury of the oral mucosa. Materials and Methods. Gene expression profiling datasets pertaining to rapid wound healing of oral mucosa were identified using the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed to identify differentially expressed genes (DEGs) during oral mucosal wound healing. Next, functional enrichment analysis was performed to identify the biological processes (BPs) and signaling pathways relevant to these DEGs. A protein-protein interaction (PPI) network was constructed to identify hub DEGs. Interaction networks were constructed for both miRNA-target DEGs and DEGs-transcription factors. A DEGs-chemical compound interaction network and a miRNA-small molecular interaction network were also constructed. Results. DEGs were found significantly enriched in several signaling pathways including arachidonic acid metabolism, cell cycle, p53, and ECM-receptor interaction. Hub genes, GABARAPL1, GABARAPL2, HDAC5, MAP1LC3A, AURKA, and PLK1, were identified via PPI network analysis. Two miRNAs, miR-34a-5p and miR-335-5p, were identified as pivotal players in the miRNA-target DEGs network. Four transcription factors FOS, PLAU, BCL6, and RORA were found to play key roles in the TFs-DEGs interaction network. Several chemical compounds including Valproic acid, Doxorubicin, Nickel, and tretinoin and small molecular drugs including atorvastatin, 17β-estradiol, curcumin, and vitamin D3 were noted to influence oral mucosa regeneration by regulating the expression of healing-associated DEGs/miRNAs. Conclusion. Genetic and epigenetic mechanisms and specific drugs were identified as significant molecular mechanisms and entities relevant to oral mucosal healing. These may be valuable potential targets for experimental research.