Integrated Characterization of ceRNA (circRNA/lncRNA/miRNA/mRNA) Regulatory Networks in a Glaesserella parasuis–Induced Mouse Meningitis Model

Abstract

Glaesserella parasuis (G. parasuis, GPS) is a known causative agent of meningitis. A growing body of research indicates that non-coding RNAs (ncRNAs) are deeply involved in modulating inflammatory responses. In our study, we profiled the expression changes in circRNAs, lncRNAs, miRNAs, and mRNAs using a G. parasuis-induced mouse meningitis model and constructed the ceRNA networks by integrated analysis of the expression data. A total of 674 circRNAs, 376 lncRNAs, 57 miRNAs, and 373 mRNAs were differentially expressed. Functional GO and KEGG analysis showed enrichment of the source genes of differentially expressed (DE) circRNAs in protein binding, tight junction, and inflammatory pathways such as NF-kappaB, PI3K–Akt, and MAPK. The target genes of DEmiRNAs were enriched in phospholipase D, calcium, Rap1, and mTOR signaling pathways, whereas those of DElncRNAs were largely connected to tight junction, cytokine–cytokine receptor interaction, inflammatory response, and immune system processes. Subsequently, the DEcircRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 177 DEcircRNAs, 20 DEmiRNAs, and 134 DEmRNAs, and the DElncRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 152 DElncRNAs, 36 DEmiRNAs, and 177 DEmRNAs. Furthermore, the differential expression of randomly selected DEcircRNAs, DElncRNAs, DEmiRNAs, and DEmRNAs was confirmed by qRT-PCR, and the results were consistent with transcriptome sequencing. As far as we know, this study is the first integrative analysis for the ceRNA regulatory networks in G. parasuis-induced mouse meningitis, providing a theoretical basis for elucidating the pathogenic mechanisms of G. parasuis infection.