Expression and bioinformatics analysis of miR-182-5p in Alzheimer's disease

ObjectiveTo investigate the expression level of miR-182-5p in the peripheral blood serum of patients with Alzheimer's disease(AD), predict its target genes and conduct functional analysis by bioinformatics methods.

MethodsThe dataset of GSE104514 was searched and downloaded from the GEO database. The differentially expressed miRNAs of the dataset were analyzed by GEO2R tool. Among which, miR-182-5p was the most differentially expressed miRNA and was selected for in-depth analysis. Fifteen normal controls(NC) and twenty-eight patients with AD were enrolled in this study. The expression levels of miR-182-5p in peripheral blood serum were determined by real-time fluorescent quantitative PCR. MiRBase database was used to analyze the conservativeness of miR-182-5p among different species. miRcode, miRDB, miRWalk and Target Scan databases were performed to predict the target genes of miR-182-5p, and the common target genes of these databases were screened out. GO and KEGG functional enrichment analysis of miR-182-5p target genes were conducted by DAVID and KOBAS databases.

ResultsThe expression of miR-182-5p in brain tissue of AD mice was higher than that in wild mice(P < 0.05). The expression level of miR-182-5p in the peripheral blood serum of AD patients(2.022±1.225) was significantly higher than that of the control group(0.486±0.442)(P < 0.01). Conservative analysis showed that the mature sequence of miR-182-5p was highly conserved in different species. A total of 23 potential intersection target genes of miR-182-5p were predicted by the online databases. The results of GO enrichment analysis suggested that the target genes of miR-182-5p were mainly enriched in zinc ion binding, negative regulation of biological process, heterocyclic compound binding, regulation of primary metabolic process, GTPase activity, intrinsic component of membrane, brain development, cell part morphogenesis, transferase activity, regulation of signaling, ubiquitin conjugating enzyme binding, cochlea development, histone H4-K16 acetylation, pharyngeal system development, neuron fate specification, cerebral cortex cell migration, and cerebral cortex radially oriented cell migration, etc. The results of KEGG signal pathway showed that target genes were mainly enriched in 5 signal pathways, including acid secretion of renal collecting tube, ether lipid metabolism, Shigellosis, adhesion of cell mucosa, and bacterial invasion of epithelial cells.

ConclusionsMiR-182-5p is highly expressed in the peripheral blood serum of AD patients and may participate in the development of AD through multiple signaling pathways.