Integrative Analysis of Deregulated miRNAs Reveals Candidate Molecular Mechanisms Linking H. pylori Infected Peptic Ulcer Disease with Periodontitis

Abstract

Objective. Periodontitis is a highly prevalent oral infectious disease and has been increasingly associated with H. pylori infection, gastric inflammation, and gastric cancer but little is known about epigenetic machinery underlying this potentially bidirectional association. The present study is aimed at identifying key deregulated miRNA, their associated genes, signaling pathways, and compounds linking periodontitis with H. pylori-associated peptic ulcer disease. Methods. miRNA expression datasets for periodontitis-affected and H. pylori-associated peptic ulcer disease-affected tissues were sought from the GEO database. Differentially expressed miRNA (DEmiRNAs) were identified and the overlapping, shared-DEmiRNA between both datasets were determined. Shared-DEmiRNA-target networks construction and functional analyses were constructed using miRNet 2.0, including shared-DEmiRNA-gene, shared-DEmiRNA-transcription factor (TF), and shared-DEmiRNA-compound networks. Functional enrichment analysis for shared DEmiRNA-gene and shared DEmiRNA-TF networks was performed using the KEGG, Reactome, and Geno Ontology (GO) pathways. Results. 11 shared-DEmiRNAs were identified, among which 9 showed similar expression patterns in both diseases, and 7 were overexpressed. miRNA hsa-hsa-mir-155-5p and hsa-mir-29a-3p were top miRNA nodes in both gene and TF networks. The topmost candidate miRNA-deregulated genes were PTEN, CCND1, MDM2, TNRC6A, and SCD while topmost deregulated TFs included STAT3, HIF1A, EZH2, CEBPA, and RUNX1. Curcumin, 5-fluorouracil, and the gallotanin 1,2,6-Tri-O-galloyl-beta-D-glucopyranose emerged as the most relevant linkage compound targets. Functional analyses revealed multiple cancer-associated pathways, PI3K pathways, kinase binding, and transcription factor binding among as enriched by the network-associated genes and TFs. Conclusion. Integrative analysis of deregulated miRNAs revealed candidate molecular mechanisms comprising of top miRNA, their gene, and TF targets linking H. pylori-infected peptic ulcer disease with periodontitis and highlighted compounds targeting both diseases. These findings provide basis for directing future experimental research.