Pathogenesis investigation of miR-199-5p in oral submucous fibrosis based on bioinformatics analysis.

ABSTRACT

OBJECTIVES: Fibrosis diseases are one of the leading causes of suffering and death. However, no systematic investigation has been carried out on fibrosis-related genes. MATERIALS AND METHODS: By querying PubMed using keywords "fibrosis" and "gene" or "protein," we identified fibrosis-related genes in the last decade. Bioinformatics analysis was performed by MAS 3.0 software. Key miRNA was selected to assess its relationship with oral submucous fibrosis (OSF) and fibroblast functions. RESULTS: A total of 1,310 genes related to fibrosis were identified. TGF-ß1, CTGF, MMP9, HSP47, and S1P were found to be associated with mainly fibrotic organs. In total, 244 cellular components terms, 595 molecular function terms, 1,816 cellular component terms, and 136 KEGG pathway annotations were predicted. miR-199-5p was selected as the key miRNA, which has higher level in OSF. Upregulated miR-199-5p was significantly related to OSF duration and OSF histological grade (p = 0.028 and 0.012, respectively). Overexpressive miR-199-5p reduced proliferation and induced apoptosis in buccal fibroblasts. Additionally, expression levels of collagen I (COL I) and III (COL III) were promoted by overexpressive miR-199-5p in buccal fibroblasts. CONCLUSION: These results indicate that fibrosis-related genes are related to a series of complex mechanisms. The characteristics of miR-199-5p may supply important clues for developing therapeutic strategy for OSF.