Gene function analysis of ATRNL1 and ceRNA network construction in Alzheimer’s disease

Abstract:

Objective To investigate and identify gene ATRNL1 function in Alzheimer’s disease（AD）.Methods Microarray data GSE36980，GSE1297，and GSE28146 were downloaded from gene expression omnibus（GEO）database. ATRNL1 differential expression of AD in Alzheimer’s disease was validated by 3 independent datasets. Meanwhile，Pearson correlation test between ATRNL1 expression and clinical data were performed. ATRNL1 co-expression gene screening and function enrichment analysis was performed by clusterProfiler，which included gene ontology（GO）and Kyoto encyclopedia of genes and genomes（KEGG）annotation. To further illustrate ATRNL1 molecule interaction detail，multiMiR package was used to download miRNA interaction，finally ATRNL1-miRNA-mRNA network was constructed for competing endogenous RNAs（ceRNA）identification of ATRNL1.Results Three isolated datasets showed ATRNL1 was significantly decreased（P<0.05）. ATRNL1 expression was significantly correlated with PMI（P<0.05），mini-mental status examination（MMSE）（P<0.001），and neurofibrillary tangles（NFT）（P<0.05）. ATRNL1 co-expression genes enrichment analysis showed that the biological process of signal release（GO：0023061），synaptic vesicle cycle（hsa04721），GABAergic synapse（hsa04727）were significantly related to ATRNL1. The constructed ATRNL1-miRNA-mRNA regulatory network found that MOAP1，WDR47，and REEP1 were found as ceRNA by competing hsa-miR-192-5p with ATRNL1.Conclusion It is discovered for the first time that ATRNL1 may affect AD occurrence through synapse signal release and GABAergic synapse，and more importantly ATRNL1 may function as ceRNA with MOAP1 by competing hsa-miR-192-5p.