An in silico approach to identify potential downstream targets of miR-153 involved in Alzheimer's disease.

Abstract

Background: In recent years, microRNAs (miRNAs) have emerged as key players in the pathophysiology of multiple diseases including Alzheimer's disease (AD). Messenger RNA (mRNA) targeting for regulation of gene expression by miRNAs has been implicated in the annotation of disease pathophysiology as well as in the explication of their starring role in contemporary therapeutic interventions. One such miRNA is miR-153 which mediates the survival of cortical neurons and inhibits plaque formation. However, the core mRNA targets of miR-153 have not been fully illustrated. Objective: The present study aimed to elucidate the potential involvement of miR-153 in AD pathogenesis and to reveal its downstream targets. Methods: miRanda was used to identify AD-associated targets of miR-153. TargetScan, PicTar, miRmap, and miRDB were further used to validate these targets. STRING 12 was employed to assess the protein-protein interaction network while Gene ontology (GO) analysis was carried out to identify the molecular functions exhibited by these gene targets. Results: In silico analysis using miRanda predicted five important AD-related targets of miR-153, including APP, SORL1, PICALM, USF1, and PSEN1. All five target genes are negatively regulated by miR-153 and are substantially involved in AD pathogenesis. A protein interaction network using STRING 12 uncovered 30 potential interacting partners for SORL1, PICALM, and USF1. GO analysis revealed that miR-153 target genes play a critical role in neuronal survival, differentiation, exon guidance, amyloid precursor protein processing, and synapse formation. Conclusion: These findings unravel the potential role of miR-153 in the pathogenesis of AD and provide the basis for forthcoming experimental studies.