Immune-Related Hub Genes and the Competitive Endogenous RNA Network in Alzheimer’s Disease

Article type: Research Article

Authors: Xu, Hui^a | Jia, Jianping^{a; b; c; d; *}

Affiliations: [a] Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China | [b] Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China | [c] Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China | [d] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China

Correspondence: [*] Correspondence to: Jianping Jia, Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, China, 100053. Tel.: +86 10 83199449; jjp@ccmu.edu.cn

Abstract: 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

DOI: 10.3233/JAD-200081

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1255-1265, 2020