TLR2, SOCS1 and IL1R1 but not Legionella Play a Potential Role in the Pathogenesis of Bell’s Palsy Revealed by Competitive Endogenous RNA Network Study

Abstract

Background: The present study aimed to identify the key long noncoding RNAs (lncRNAs) and determine their potential etiological factors of Bell’s palsy using RNA-Seq data based on bioinformatics tools. Methods: Serum from fifteen patients with Bell’s palsy and fifteen healthy individuals were collected. Differentially Expressed Genes (DEGs)-Differentially Expressed lncRNAs (DELs) in two groups were identified. The competing endogenous RNAs (ceRNAs) regulatory network was constructed by integrating lncRNA-mRNA pairs, miRNA-mRNA regulatory pairs, and miRNA-lncRNA pairs using Cytoscape. The Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses of key lncRNAs in the ceRNA network were evaluated to explore the effects of lncRNA during the occurrence of Bell’s palsy. Finally, pathogen culture, ELISA or q-PCR were applied to verify the presence of the pathogen and relevant cytokines or proteins. Results: In the present study, hub proteins such as TLR2 (degree=25), ITGAM (degree=14), SOCS1 (degree=13), IL1R1 (degree=11) were identified in PPI network based on DEGs. Subsequently, 2761 lncRNA-mRNA coexpression pairs including RP11-415J8.3-TLR2, 5629 miRNA-lncRNA interaction pairs, and 51 miRNA-mRNA interactions were obtained. Finally, 9 miRNAs, 5 DEGs, 6 DELs, and 9 miRNA-mRNA pairs, 10 miRNA-lncRNA pairs, and 7 mRNA-lncRNA co-expression pairs were including in ceRNA regulatory network. Meanwhile, RP11-415J8.3 were mainly enriched to legionellosis (pathway), cytokine receptor activity (GO: 0004896), and phospholipid binding (GO: 0005543). Subsequently, validation of neuroinflammation relevant TLR2, ITGAM, SOCS1, IL1R1 and legionella through another forty-five BP patients and thirty healthy individuals showed that TLR2, ITGAM, IL1R1 expressions were upregulated in the serum of patients with Bell’s palsy while SOCS1 was down-regulated, while legionella was not found among them. Conclusions: We hypothesized that the etiological factor of Bell’s palsy correlate to a complex miRNA-lncRNA-mRNA interacting network and IL1R1, SOCS1 and TLR2 may involve in the onset of Bell’s palsy rather than legionella.