MicroRNA-4722-5p and microRNA-615-3p serve as potential biomarkers for Alzheimer's disease.

Abstract

The aim of the present study was to investigate the expression levels of microRNA(miR)-4722-5p and miR-615-3p in Alzheimer's disease (AD) and their diagnostic value. Blood samples were collected from 33 patients with AD and 33 healthy controls, and an β-amyloid (Aβ)25-35-induced PC12 cell model was also established. The relative mRNA expression levels of miR-4722-5p and miR-615-3p were detected using reverse transcription-quantitative PCR. The correlations between the mRNA expression levels of the two miRNAs and the mini-mental state examination (MMSE) scores were analyzed, and the receiver operating characteristic curve was used to assess the diagnostic value of miR-4722-5p and miR-615-3p in AD. Functional enrichment analysis of the miRNA target genes was performed using The Database for Annotation, Visualization and Integrated Discovery database and the R language analysis package. The mRNA expression levels of miR-4722-5p and miR-615-3p were increased in patients with AD and the Aβ25-35-induced PC12 cell model. The mRNA expression levels of miR-4722-5p and miR-615-3p were negatively correlated with MMSE scores, and the combination of the two miRNAs for AD had an improved diagnostic value than that of each miRNA alone. The results of Gene Ontology (GO) enrichment analysis showed that the target genes of miR-4722-5p were found in the cytoplasm and cytosol, and were mainly involved in protein folding and cell division. The molecular functions included protein binding and GTPase activator activity. The results of Kyoto Encyclopedia of Genes and Genomes analysis showed that miR-4722-5p was associated with the regulation of dopaminergic synapses and mTOR signaling pathways. GO enrichment analysis also revealed that the target genes of miR-615-3p were located in the nucleus and cytoplasm, were involved in the regulation of transcription and protein phosphorylation, and were associated with protein binding, metal ion binding and transcription factor activity. The target genes of miR-615-3p played important roles in the regulation of the Ras and FoxO signaling pathways. In conclusion, miR-4722-5p and miR-615-3p may be potential biomarkers in the early diagnosis of AD.