Bioinformatics analysis constructs potential ferroptosis-related ceRNA network involved in the formation of intracranial aneurysm

Background: Intracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA.

Materials and methods: To identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues.

Results: Iron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed.

Conclusion: CeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.