Identification of Competing Endogenous RNA Networks and Potential Therapeutic Drugs for Gastroesophageal Reflux Disease

Abstract

Background: The diagnosis and cure rate of gastroesophageal reflux disease (GERD) is low, and its pathogenesis remains unclear. Aims: In this study, we aimed to construct the competing endogenous RNA (ceRNA) of GERD by bioinformatics and explore the potential therapeutic drugs for GERD. Methods: The differentially expressed genes (DEGs) were got by limma package and visualized by ggplot2 and pheatmap package in R version 4.1.3 from the GSE63401 gene microarray data. The pro-tein-protein interaction (PPI) network was constructed by the STRING database. The hub genes and subnetwork modules were obtained by Cytoscape software. The microRNA and lncRNA were pre-dicted by the miRTarBase and miRNet databases to construct the ceRNA network. Potential drugs tar-geting DEGs were screened by the CMAP database. Results: In this study, a total of 571 GEDs were obtained, including 462 up-regulated genes and 109 down-regulated genes, which mainly participated in the leukocyte migration process and the cytokine-cytokine receptor interaction pathway. Seventeen miRNAs and three key lncRNAs involved in regulat-ing hub genes were screened through miRTarBase and miRNet databases. Finally, nine ceRNA net-works were obtained, including TTN-AS1/NEAT1/XIST - miR-139-5p - CXCR4 axis, TTN-AS1/NEAT1/XIST - miR-185-5p - IL1B axis and TTN-AS1/NEAT1/XIST - miR-495-3p - LYN axis. In addition, five potential drugs (Pimavanserin, BMS-182874, CL-218872, Losartan, and Laropiprant) for GERD were obtained through the CMAP database. Conclusion: We constructed nine GERD-related ceRNA networks and screened five potential thera-peutic drugs for GERD, providing a theoretical basis for further research on the pathogenesis of GERD.