Abstract
PURPOSE: The goal of this study was to identify the crucial autophagy-related genes (ARGs) in periodontitis and construct mRNA-miRNA-lncRNA networks to further understand the pathogenesis of periodontitis. METHODS: We used the Gene Expression Omnibus (GEO) database and Human Autophagy Database (HADb) to identify differentially expressed mRNAs, miRNAs, and ARGs. These ARGs were subjected to Gene Ontology (GO), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, and PPI (protein-protein interaction) network analysis. Two databases (miRDB and StarBase v2.0) were used to reverse-predict miRNAs while the miRNA-lncRNA interaction was predicted using the StarBase v2.0 and LncBase Predicted v.2 databases. After excluding the lncRNAs only present in the nucleus, a competing endogenous RNA (ceRNA) network was built. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the levels of mRNA expression in the ceRNA network. RESULTS: The differential expression analysis revealed 10 upregulated and 10 downregulated differentially expressed ARGs. After intersecting the reverse-predicted miRNAs with the differentially expressed miRNAs, a ceRNA network consisting of 4 mRNAs (LAMP2, NFE2L2, NCKAP1, and EGFR), 3 miRNAs (hsa-miR-140-3p, hsa-miR-142-5p, and hsa-miR-671-5p), and 30 lncRNAs was constructed. In addition, qRT-PCR results revealed that EGFR expression was downregulated in diseased gingival tissue of periodontitis patients. CONCLUSION: Four autophagy-related genes, especially EGFR, may play a key role in periodontitis progression. The novel ceRNA network may aid in elucidating the role and the mechanism of autophagy in periodontitis, which could be important in developing new therapeutic options.