Mirnas regulating the expressions of ntf3, gng2 and itga7 are involved in the pathogenesis of abdominal aortic aneurysm in mice

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, but effective treatment strategies remain lacking. The objective of this study was to screen underlying therapeu-tic targets by investigating the molecular mechanisms of AAA using mouse models. The mRNA (GSE109639) and miRNA (GSE51229 and GSE54943) expression profiles of mouse AAA models were downloaded from Gene Expression Omnibus database. A total of 1367 differentially expressed genes (DEGs) were identified between AAA and sham group, 490 of which were used for constructing the Protein-Protein Interaction (PPI) network. NTF3, GNG2 and ITGA7 in the PPI network were suggested to be hub genes according to their ranking of topological features. Furthermore, hub gene GNG2 was enriched in module 1, while ITGA7 was enriched in module 3. Eighteen differentially expressed miRNAs (DEMs) were shared in two datasets, 6 of which were predicted to regulate 130 DEGs (i.e. mmu-miR-677-ITGA7, mmu-miR-350-NTF3 and mmu-miR-292-3p-GNG2) to establish the miRNA-mRNA regulatory network. Function enrichment analysis showed NTF3 was involved in cell motion and MAPK signaling pathway; ITGA7 affected extracellular matrix (ECM)-receptor interaction; GNG2 participated in cell proliferation and chemokine signaling pathway. In conclusion, miRNAs regulating the expressions of NTF3, GNG2 and ITGA7 may represent underlying targets for treatment of AAA.