Autophagy-Related Genes Predict the Progression of Periodontitis Through the ceRNA Network

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.

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

“…42 Mengyao Bian et al analyzed the GSE10334, GSE16134, and GSE54710 datasets and found that EGFR expression levels in diseased gingival tissues from periodontitis patients were significantly lower than those in healthy individuals. 1 However, there are few bioinformatics analyses related to the osteogenic differentiation of hPDLSCs in inflammatory environments.…”

“…Periodontitis caused by dental plaque biofilms and inflammations usually lead to the destruction of periodontal tissues, including periodontal ligaments, alveolar bone, and cementum. [1][2][3] Numerous studies have shown that severe periodontitis is caused by excessive immune response, but the process of excessive immune response and the specific mechanism of its surrounding periodontal tissue damage are still unclear. [4][5][6] The exploration of pathogenesis of periodontitis has never stopped, and the latest research has shown that fibrin deposition is the culprit of severe periodontitis and an important target for stopping the alveolar bone damage caused by severe periodontitis.…”

“…Periodontitis caused by dental plaque biofilms and inflammations usually lead to the destruction of periodontal tissues, including periodontal ligaments, alveolar bone, and cementum 1–3 . Numerous studies have shown that severe periodontitis is caused by excessive immune response, but the process of excessive immune response and the specific mechanism of its surrounding periodontal tissue damage are still unclear 4–6 .…”

A review on the role of miR-671 in human disorders

“…A high throughput sequencing study in pseudoexfoliation syndrome has led to identification of four aberrantly expressed miRNAs among them being miR-671-3p ( Tomczyk-Socha et al, 2022 ). miR-671-5p has also been among miRNAs participating in the pathogenesis of periodontitis through establishment of ceRNA regulatory network regulating autophagy ( Bian et al, 2022 ). miR-671 has also been found to be down-regulated in patients with rheumatoid arthritis ( Tang et al, 2019 ), hand, foot, and mouth disease ( Lin et al, 2020 ), placenta accreta spectrum ( Chen et al, 2020b ), coronary artery disease ( Zhong et al, 2020 ), Parkinson’s disease ( Uwatoko et al, 2019 ) and Kawasaki disease ( Zhang et al, 2018 ).…”

Identification and validation of autophagy-related genes in Kawasaki disease

“…Autophagy is an evolutionarily conserved catabolic process that maintains the dynamic balance of the internal environment [4]. Under the regulation of autophagyrelated genes (ARGs), intracellular bilateral membrane structures encapsulate substances and organelles to be degraded and thereby form autophagosomes, which then fuse with lysosomes, forming autolysosomes, which perform cellular metabolism through the action of hydrolytic enzymes [5]. A previous study has shown that autophagy is related to inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, and cancer [6].…”