Integrated analysis of miRNA and mRNA expression in the blood of patients with Alzheimer's disease

Abstract

alzheimer's disease (ad) is a progressive neurodegenerative disease, which is considered the most common type of dementia worldwide. The aim of the present study was to identify key micrornas (mirnas/mirs) and mrnas affecting the pathogenesis of ad, which may be developed as promising biomarkers for the early diagnosis or targeted therapy of patients with ad. integrative analysis was performed on 12 representative mirna datasets and three mrna datasets of the blood from patients with ad, in order to identify differentially expressed (de)mirnas and demrnas. Subsequently, the mirWalk database was used to identify the potential mirna-mrna interactions among demirnas and DEmRNAs, and an AD-specific miRNA-mRNA network was constructed using cytoscape software. Gene ontology and Kyoto encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the target mrnas of demirnas. a total of 37 demirnas and 2,011 demrnas were identified between AD and normal control samples. In addition, 853 high confidence miRNA-mRNA interactions were identified and subsequently used to construct the AD specific miRNA-mRNA network. A total of five miRNAs, including hsa-mir-93, hsa-mir-26b, hsa-mir-34a, hsa-mir-98-5p and hsa-miR-15b-5p were identified as the key nodes in the mirna-mrna network by topological analysis. Functional enrichment analysis demonstrated that the target mrnas of demirnas were enriched in ad-associated pathways, such as the 'neurotrophin signaling pathway' and 'insulin signaling pathway'. Taken together, the results of the present study provide novel insights into the molecular mechanisms underlying ad and contribute to the identification of biomarkers and novel strategies for drug design for ad treatment.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…In addition, when conducting a genome-wide serum microRNA screening with NGS, and subsequent RT–PCR, on a discovery cohort and a validation cohort, six miRNAs were differentially expressed between patients and controls (miR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p), with miR-342-3p presenting the highest sensitivity and specificity [ 237 ]. Results from an integrated analysis conducted on 12 miRNA datasets identified 37 dysregulated miRNAs in AD compared to controls, with has-miR-93, has-miR-26b, has-miR-34a, has-miR-98-5p, and has-miR-15b-5p being the key nodes when analyzing miRNA–mRNA interactions and modulation [ 238 ]. Notably, machine learning techniques can also be applied to analyze peripheral blood miRNA signatures, with recent data proposing machine learning models reaching up to 92% and 90,9% accuracy in the serum and plasma, respectively [ 239 ].…”

Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in Alzheimer’s disease

“…CD70 has been shown as a promising biomarker in multiple sclerosis [181], but this gene might be novel target for AD. Hsa-mir-378a-3p [182], hsa-mir-100-5p [182], hsa-mir-27a-3p [183], hsa-mir-15b-5p [184], hsa-mir-320d [185], NRF1 [186], STAT1 [187], YY1 [188], PPARG (peroxisome proliferator-activated receptor gamma) [189] and TP53 [190] have been shown to be an important role in AD. MYB (MYB proto-oncogene, transcription factor), ANLN (anillin actin binding protein), SERPINH1, LATS2, DCLK1, TP63, LCK (LCK proto-oncogene, Src family tyrosine kinase), hsa-mir-513a-5p, hsa-mir-138-1-3p, hsa-mir-548d-5p, hsa-mir-4726-3p, hsa-mir-1202, E2F6, ZNF354C, ARID3A, FOXL1 and RUNX2 might be the novel biomarkers for AD.…”

Post‐transcriptional regulation of α7 nAChR expression by miR‐98‐5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease

“…MiR‐98‐5p is a highly conserved RNA molecule that is widely expressed among various tissues of mammals. A recent genome‐wide miRNA profiling analysis has shown the dysregulation of miR‐98‐5p in the serum of AD patients and identified miR‐98‐5p as a keynote in AD specific miRNA‐mRNA network 34,35 . Moreover, two in vitro investigations have reported the regulatory role of miR‐98‐5p on Aβ production by targeting IGF‐1 and SNX6, 36,37 indicating that miR‐98‐5p may function at a certain extent in the pathology of AD.…”