MicroRNA expression data analysis to identify key miRNAs associated with Alzheimer's disease

Abstract

Background: MicroRNAs (miRNAs) have become increasingly prevalent as a result of the association of their deregulation with neurodegenerative disorders, especially Alzheimer's disease (AD). However, the association between miRNAs and AD remains unclear. Methods: In the present study, Nine representative miRNA datasets were selected for the identification of the critical miRNAs by analyzing the overlapping relationships among them. TargetScan software (http://www.targetscan.org) was used to predict the target genes of these miRNAs. In addition, the Database for Annotation Visualization and Integrated Discovery (DAVID; http://david.abcc.ncifcrf.gov) and TfactS (http://www.tfacts.org) datasets were used for combined analysis of functional enrichment and transcription factor (TF) analysis. Results: Thirteen key miRNAs were identified, of which four were significantly up-regulated (hsa-miR-101,hsa-miR-155, has-miR-34a, has-miR-9) and eight were found to be significantly down-regulated (hsa-let-7d-5p, hsa-let-7 g-5p, hsa-miR-15b, has-miR-191-5p, hsa-miR-125b, has-miR-26b-5p, hsa-miR-29b, hsa-miR-342-3p). The functional enrichment analysis indicated that up-regulated signature miRNA targets were associated with transcription from the RNA polymerase II promoter process and the chemical synaptic transmission process. Down-regulated signature miRNA targets were mostly enriched with respect to positive regulation of transcription from the RNA polymerase II promoter process, p53 signaling, and microRNAs in cancer pathways. TF analysis showed that 87 TFs were influenced by the up-regulated miRNAs, and 134 TFs were influenced by the down-regulated miRNAs. In total, 70 (45.5%) TFs were affected by both up-regulated and down-regulated miRNAs. Conclusions: In summary, 13 key miRNAs were found to have a vital function in the pathological progress of AD, as well as the target genes and TFs of these miRNAs. The potential functions of these miRNAs as diagnostic and therapeutic targets of the AD are revealed by the present study.