Differential expression profile of circular RNA in brain tissue of APP/PS1 transgenic mice and its related ceRNA construction

ObjectiveTo explore the differential expression profile of circular RNA (circRNA) in brain tissue of Alzheimer's disease (AD) model mouse, to construct circRNA-miRNA-mRNA regulatory network, and to clarify the regulatory mechanism of circRNA in the occurrence of AD.

MethodsThe differential expression of circRNA in the brain of APP/PS1 transgenic AD model mice was analyzed by gene microarray.Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed on the differential circRNAs.Real-time quantitative polymerase chain reaction was used to verify the randomly selected 5 differentially expressed circRNAs, and circRNA-miRNA-mRNA was constructed to perform AD target gene function prediction analysis.

ResultsA total of 52 differentially expressed circRNAs were screened, of which 28 were up-regulated and 24 were down-regulated.The enrichment analysis results of GO and KEGG showed that the differentially expressed parental genes of circRNAs were mainly involved in nervous system development, protein binding, RNA transport, signaling pathways regulating stem cell pluripotency, and Hippo signaling pathways.Biological information was used to analyze the successfully constructed competing endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA, indicating that the enriched functions of these target genes might play a role through small molecule binding, plasma membrane, cAMP signaling pathway, and Rap1 signaling pathway.

ConclusionsThere are various differentially expressed circRNAs in the brain of AD model mice, and these differentially expressed genes may be involved in the molecular regulation of AD occurrence through the circRNA-miRNA-mRNA regulatory network.