Study on the Mechanism of PSMC6 Gene in Alzheimer’s Disease Based on circRNA-miRNA-mRNA Regulatory Network Analysis

The role of circular RNA (circRNA) and microRNA (miRNA) as potential biomarkers in Alzheimer’s disease (AD). The Gene Expression Omnibus (GEO) database is used to obtain expression profiles of Alzheimer’s disease patients (GSE4226, GSE97760, GSE147232, GSE161435, and GSE186929). Preliminary data screening was conducted using R software to identify significantly different circRNAs, miRNAs, and mRNAs. The differentially expressed genes were subjected to GO and KEGG enrichment analysis, and the circRNAs and mRNAs involved in the interaction between differentially expressed miRNAs were predicted. A circRNA-miRNA-mRNA regulatory network was constructed. 63 significantly different mRNAs, 199 significantly different miRNAs, and 55 significantly different circRNAs were identified. GO and KEGG enrichment analysis was performed on differential mRNAs to obtain Proteasome 26S Subunit 6 (PSMC6) and Kinase 1 Alpha 1 (CSNK1A1) enriched in Alzheimer’s disease. Eight key circRNAs, 56 mRNAs, and 123 miRNAs were selected through prediction and database screening. miRNAs and circRNAs that interact with the core PSMC6 were selected to construct a core competitive endogenous RNA (ceRNA) network for differential expression in peripheral blood of Alzheimer’s disease patients. We found that the regulation of circRNA can lead to changes in the expression of a large number of miRNAs, which further affects the expression of key mRNA (PSMC6) and leads to Alzheimer’s disease pathology. The molecular mechanism of PSMC6 gene regulated by circRNA-miRNA-mRNA network in Alzheimer’s disease has been deeply revealed, enriching the understanding of the pathogenesis of Alzheimer’s disease and providing new perspectives and ideas for theoretical research in this field.