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- Academic Editor
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Background: Alzheimer’s disease (AD) occurs in the elderly and
pre-elderly, characterized by decline of memory, cognitive dysfunction,
impairment of learning capacity, and motor dysfunction. Recently a competitive
endogenous RNA (ceRNA) network has been found to be related to AD progression,
but there is still little understanding of the ceRNA regulatory network in AD.
This study aims to explore the important regulatory mechanisms of ceRNA
regulatory networks containing long non-coding RNAs (lncRNAs), circular RNAs
(circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in AD.
Methods: Data from the gene expression omnibus (GEO) database were used
for the analysis. To study enrichment function for the upregulated and
downregulated mRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
Genomes (KEGG) enrichment analyses were performed using the Metascape database,
respectively. Based on the STRING database and Cytoscape
software 3.9.1, a protein-protein interaction (PPI) network was constructed. The
hub genes in this network were identified utilizing the CytoHubba plugin in
Cytoscape. The TargetScan, miRWalk, and miRDB were selected to calculate the
regulatory interaction between miRNAs and the hub genes. LncRNAs were predicted
using RNA22. Additionally, circRNA prediction was executed using the circBank
database. Results: 711
downregulated and 670 upregulated overlapping mRNAs were identified between AD
and control samples. 32 downregulated and 340 upregulated miRNAs were obtained
from AD samples compared with control samples. 78 upregulated and 205
downregulated circRNAs were screened. 275 upregulated lncRNAs and 209
downregulated lncRNAs were found between AD samples and control samples. The PPI
network constructed consists of 1016 nodes and 13,946 edges. Ten hub genes were
selected to identify target miRNAs and ceRNAs. On the basis of the ceRNA
hypothesis, a circRNA/lncRNA-miRNA-mRNA network was established. It included five
lncRNAs (TRHDE-AS1, SNHG10, OIP5-AS, LINC00926 and LINC00662), 26 circRNAs, five
miRNAs (hsa-miR-3158-3p, hsa-miR-4435, hsa-let-7d-3p, hsa-miR-330-5p and
hsa-miR-3605-3p), and ten mRNAs (RPL11, RPL34, RPL21, RPL22, RPL6, RPL32, RPL24,
RPL35, RPL31, and RPL35A). RPL35 and RPL35A were found to be significantly
associated with AD pathology in tau and A