Background: The pathogenesis of Alzheimer's disease (AD) involves various immune-related phenomena; however, the mechanisms underlying these immune phenomena and the potential hub genes involved therein are unclear. An understanding of AD-related immune hub genes and regulatory mechanisms would help develop new immunotherapeutic targets.
Objective: The aim of this study was to explore the hub genes and the mechanisms underlying the regulation of competitive endogenous RNA (ceRNA) in immune-related phenomena in AD pathogenesis.
Methods: We used the GSE48350 data set from the Gene Expression Omnibus database and identified AD immune-related differentially expressed RNAs (DERNAs). We constructed protein-protein interaction (PPI) networks for differentially expressed mRNAs and determined the degree for screening hub genes. By determining Pearson's correlation coefficient and using StarBase, DIANA-LncBase, and Human MicroRNA Disease Database (HMDD), the AD immune-related ceRNA network was generated. Furthermore, we assessed the upregulated and downregulated ceRNA subnetworks to identify key lncRNAs.
Results: In total, 552 AD immune-related DERNAs were obtained. Twenty hub genes, including PIK3R1, B2M, HLA-DPB1, HLA-DQB1, PIK3CA, APP, CDC42, PPBP, C3AR1, HRAS, PTAFR, RAB37, FYN, PSMD1, ACTR10, HLA-E, ARRB2, GGH, ALDOA, and VAMP2 were identified on PPI network analysis. Furthermore, upon microRNAs (miRNAs) inhibition, we identified LINC00836 and DCTN1-AS1 as key lncRNAs regulating the aforementioned hub genes.
Conclusion: AD-related immune hub genes include B2M, FYN, PIK3R1, and PIK3CA, and lncRNAs LINC00836 and DCTN1-AS1 potentially contribute to AD immune-related phenomena by regulating AD-related hub genes.
Keywords: Alzheimer’s disease; competitive endogenous RNA; hub genes; immune system.