Differential expression and functional analysis of circular RNA in Alzheimer’s disease

This study investigated the pathogenesis of Alzheimer’s disease by analyzing the differential expression of circular RNAs (circRNAs), and their interactions with microRNAs (miRNAs). A circRNA microarray was used to screen expressed circRNAs in peripheral blood leukocytes from three patients with AD and four healthy control participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate the functions of the circRNAs. Changes in expression of six circRNAs [0045808/0070162/0001929/0092270/0092222/0092223]) was confirmed by RT-qPCR, of which three (hsa_circ_[0045808/0070162/0092270]) were further verified by RT-qPCR using a large sample of 23 patients with AD and 25 healthy controls. A circRNA-miRNA-mRNA interaction network, constructed using TargetScan, miRanda, and Cytoscape, revealed upregulated (n=311) and downregulated (n=433) circRNAs, whereaswhile 443 circRNAs were downregulated. GO and KEGG analyses associated differentially expressed circRNAs to neurotransmitters, cell senescence, P53, mTOR, and PI3K-AKT. Microarray sample verification using RT-qPCR confirmed the microarray analysis results on changes in the six circRNAs. Contrary to the microarray analysis, large-sample verification of significantly elevated circRNA expression was partially consistent (hsa_circ_0092270), and inconsistent (hsa_circ_0045808, hsa_circ_0070162), with the microarray results. The findings highlight the significance of circRNAs in AD and that hsa_circ_0092270 represents a promising biomarker for future studies. The circRNA microarray was used to screen the differentially expressed circRNAs in peripheral blood leukocytes from 3 patients with AD and 4 healthy control participants