Research of circRNA Expression in Serum of Patients with Alzheimer Disease by High-Throughput Sequencing

GUO Qingyun; CUI Jian; WU Rui

doi:10.3969/j.issn.1004-437X.2025.04.005

Abstract：Objective To detect the difference of circRNA expression profile in the serum of Alzheimer disease(AD)patients by high-throughput sequencing and find the potential diagnostic biomarkers of AD in combination with clinical diagnosis.Methods There were 28 AD patients(AD group)and 28 healthy individuals(normal control group)were recruited.High throughput sequencing was used to test whole blood circRNA and screen differential expressed circRNA.The gene ontology database enrichment analysis(GO enrichment analysis)and signal pathway significance analysis(KEGG analysis)of signaling pathways choose the genetic variations of AD were used to analyze the differentially expressed circRNAs.Differential genes of AD were analyzed and selected,and circ 0089972 and miR-7 with significantly increased expression were detected through bioinformatics analysis,and their internal relationship was found out,and verified by double luciferase method.Results This study found that there were 29 circrnas with significant differentially expressed expression in the serum of AD patients,of which 20 were up-regulated and 9 were down-regulated(P＜0.05).GO enrichment analysis results show that the circRNA main enrichment of differentially expressed in cell metabolism,protein,organic metabolism,cell activity regulation,nitrogen metabolism,cell response to stimuli,organic combination of ring compound,ion combination,metabolism regulation,cell communication,signal transmission and other biological process.KEGG analysis showed that differential genes were mainly involved in the regulation of cancer pathways,PI3K-Akt signaling pathway,human papilloma virus infection,microRNA,MAPK signaling pathway,Ras signaling pathway,EB virus infection and other signaling pathways.The result of bioinformatics and dual-luciferase assay showed that circ_0089972 could be used as a molecular sponge(can interact with RNA molecules,competitively adsorb micrornas,and regulate miRNA levels and/or activity)to adsorb and down-regulate the expression of miR-7,thus participating in the pathophysiological process of AD.Conclusion There are significantly differentially expressed circRNAs in the serum of AD patients,and the differentially expressed circRNAs are involved in the regulation of multiple biological processes and signaling pathways of AD through their target genes.HSA_circ_0089972 and other circRNAs may be used to be the potential diagnostic biomarker of AD.