Related Network and Differential Expression Analyses Identify Nuclear Genes and Pathways in the Hippocampus of Alzheimer Disease

Abstract

Background: Alzheimer disease (AD) is a typical progressive and destructive neurodegenerative disease that has been studied extensively. However, genetic features and molecular mechanisms underlying AD remain unclear. Here we used bioinformatics to investigate the candidate nuclear genes involved in the molecular mechanisms of AD. Material/Methods: First, we used Gene Expression Omnibus (GEO) database to obtain the expression profiles of the mRNAs from hippocampus microarray and identify differentially expressed genes (DEGs) the plier algorithm. Second, functional annotation and visualization of the DEGs were conducted by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, BioGRID, IntAct, STRING, and Cytoscape were utilized to construct a protein-protein interaction (PPI) network. Hub genes were analytically obtained from the PPI network and the microRNA (miRNA)-target network. Results: Two hippocampus microarrays (GSE5281 and GSE48350) were obtained from the GEO database, comprising 161 and 253 cases separately. Among these, 118 upregulated genes and 694 downregulated genes were identified. The upregulated DEGs were mainly involved in positive regulation of transcription from RNA polymerase II promoter, positive regulation of cartilage development, and response to wounding. The downregulated DEGs were enriched in chemical synaptic transmission, neurotransmitter secretion, and learning. By combining the results of PPI and miRNA-target network, 8 genes and 2 hub miRNAs were identified, including YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, BRWD1, and hsa-miR-106b-5p and hsa-miR-93-5p. These target genes are highly enriched in various key pathways, such as amyloid-beta formation, regulation of cardiocyte differentiation, and actin cytoskeleton reorganization. Conclusions: In this study, YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, and BRWD1 were identified as candidate genes for future molecular studies in AD, which is expected to improve our understanding of its cause and potential molecular mechanisms. Nuclear genes, DEGs, and related networks identified by integrated bioinformatics analysis may serve as diagnostic and therapeutic targets for AD.

HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes

“…Cross-correlations analyses of circRNAs in HuD-OE and HuD-KO mice confirmed that the expression of multiple circRNAs correlate with HuD levels in the cell. These include circRNAs from genes associated with neurodevelopmental disorders and Alzheimer’s disease, e.g., circBrwd1 and circFoxp1 ( Bacon et al, 2015 ; Quan et al, 2020 ); involved in neuronal development and regeneration, e.g., circMap1a ( Nunez and Fischer, 1997 ) and, encoding members of the Plasticity Related Genes (PRGs) and membrane-associated guanylate kinases (MAGUKs) families, e.g., circMagi1 and circLppr4 , respectively, which control synaptic development and are linked to psychiatric disorders ( Ito et al, 2012 ; Yu et al, 2015 ). Interestingly, circFoxp1 and circMap1a are part of ceRNA networks involving miRNAs, such as miR-125a-5p, which was previously associated with aging ( Makwana et al, 2017 ) and several protein-coding genes controlling neuronal polarity and cellular differentiation, such as Camsap3 and Ebf1 ( Garel et al, 1999 ; Pongrakhananon et al, 2018 ).…”

Microarray Analysis Identifies Key Differentially Expressed Circular RNAs in Aged Mice With Postoperative Cognitive Dysfunction

“…Prkacb may be modified by circRNA_22673. Egfr has also been proposed as a fundamental disease-associated protein in AD pathogenesis (Quan et al, 2020;Yuen et al, 2020). They have therapeutic abilities through autophagy induction and the attenuation of reactive astrocytes (Tavassoly et al, 2020).…”

Estradiol exerts a neuroprotective effect on SH‐SY5Y cells through the miR‐106b‐5p/TXNIP axis

“…Several research studies indicated that miR-106, which is related to the dysfunction of synaptic and the AD-related cognitive deficits, might target tau-phosphorylating Fyn-kinase. [38][39][40] Another differential expression analysis on differentially expressed genes in the hippocampus of AD identified miR-106b as a hub miRNA, [41] suggesting the further role of miR-106b in neuron protection through targeting other downstream genes. Here, miR-106b inhibits the expression level of TXNIP via direct binding to its 3′-UTR, indicating that miR-106b might also contribute to the neuroprotective effect of estradiol in a TXNIP-related way.…”