Construction of lncRNA-ceRNA Networks to Reveal the Potential Role of Lfng/Notch1 Signaling Pathway in Alzheimer's Disease.

Abstract

Background: Alzheimer's disease (AD) develops through a complex pathological process, in which many genes play a synergistic or antagonistic role. LncRNAs represent a kind of noncoding RNA, which can regulate gene expression at the epigenetic, transcriptional and posttranscriptional levels. Multiple lncRNAs have been found to have important regulatory functions in AD. Thus, their expression patterns, targets and functions should be explored as therapeutic targets.

Methods: We used deep RNA-seq analysis to detect the dysregulated lncRNAs in the hippocampus of APP/PS1 mice. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to predict the biological roles and potential signaling pathways of dysregulated lncRNAs. Finally, we constructed lncRNA-miRNA-mRNA and lncRNA-mRNA co-expression networks to reveal the potential regulator roles in AD pathogenesis.

Results: Our findings revealed 110 significantly dysregulated lncRNAs. GO and KEGG annotations showed the dysregulated lncRNAs to be closely related to the functions of axon and protein digestion and absorption. The lncRNA-mRNA network showed that 19 lncRNAs regulated App, Prnp, Fgf10 and Il33, while 5 lncRNAs regulated Lfng via the lncRNA-miR-3102-3p-Lfng axis. Furthermore, we preliminarily demonstrated the important regulatory role of the Lfng/Notch1 signaling pathway through lncRNA-ceRNA networks in AD.

Conclusion: We revealed the important regulatory roles of dysregulated lncRNAs in the etiopathogenesis of AD through lncRNA expression profiling. Our results showed that the mechanism involves the regulation of the Lfng/Notch1 signaling pathway.