Identification of microRNA-mRNA Regulatory Networks with Therapeutic Values in Alzheimer’s Disease by Bioinformatics Analysis

Article type: Research Article

Authors: Kavoosi, Sakine^a | Shahraki, Ali^{a; *} | Sheervalilou, Roghayeh^{b; *}

Affiliations: [a] Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran | [b] Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

Correspondence: [*] Correspondence to: Roghayeh Sheervalilou, Assistant Prof. of Molecular Medicine, Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran. Tel.: +985433295705; Fax: +985433295705; E-mail: sheervalilour@tbzmed.ac.ir, ORCID: 0000-0001-7996-845X and Ali Shahraki, Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran. E-mail: ashahraki@science.usb.ac.ir.

Abstract: Background:Alzheimer’s disease (AD) is the most prevalent neurological disorder worldwide, affecting approximately 24 million individuals. Despite more than a century of research on AD, its pathophysiology is still not fully understood. Objective:Recently, genetic studies of AD have focused on analyzing the general expression profile by employing high-throughput genomic techniques such as microarrays. Current research has leveraged bioinformatics advancements in genetic science to build upon previous efforts. Methods:Data from the GSE118553 dataset used in this investigation, and the analyses carried out using programs such as Limma and BioBase. Differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRs) associated with AD identified in the studied areas of the brain. Target genes of the DEmiRs identified using the MultiMiR package. Gene ontology (GO) completed using the Enrichr website, and the protein-protein interaction (PPI) network for these genes drawn using STRING and Cytoscape software. Results:The findings introduced DEGs including CTNNB1, PAK2, MAP2K1, PNPLA6, IGF1R, FOXL2, DKK3, LAMA4, PABPN1, and GDPD5, and DEmiRs linked to AD (miR-106A, miR-1826, miR-1253, miR-10B, miR-18B, miR-101-2, miR-761, miR-199A1, miR-379 and miR-668), (miR-720, miR-218-2, miR-25, miR-602, miR-1226, miR-548K, miR-H1, miR-410, miR-548F2, miR-181A2), (miR-1470, miR-651, miR-544, miR-1826, miR-195, miR-610, miR-599, miR-323, miR-587 and miR-340), and (miR-1282, miR-1914, miR-642, miR-1323, miR-373, miR-323, miR-1322, miR-612, miR-606 and miR-758) in cerebellum, frontal cortex, temporal cortex, and entorhinal cortex, respectively. Conclusions:The majority of the genes and miRNAs identified by our findings may be employed as biomarkers for prediction, diagnosis, or therapy response monitoring.

Keywords: Alzheimer’s disease, bioinformatics, microRNA (miRNA or miR)-mRNA regulatory network, nanoparticles, protein-protein interaction

DOI: 10.3233/JAD-230966

Journal: Journal of Alzheimer's Disease, vol. 98, no. 2, pp. 671-689, 2024