Identification and interaction analysis of hubgenes related to neutrophil ferroptosis in intracranial atherosclerotic stenosis.

Circulating neutrophils and ferroptosis are vital for the development of intracranial atherosclerotic stenosis (ICAS). This study aimed to explore that whether neutrophil ferroptosis participate in ICAS. Sixteen patients with ICAS and 14 healthy controls were enrolled. We collected peripheral blood and separated neutrophils. LncRNA, mRNA, and miRNA sequencing were performed. The differently expressed (DE) lncRNAs, mRNAs, and miRNAs were selected. The protein-protein interaction (PPI) network was constructed, top 30 hubgenes were selected, and intersected with DE ferroptosis genes to obtain the core genes. Combined with DE lncRNAs and miRNAs, the ceRNA network and TF-miRNA-mRNA network were constructed. Finally, the expression levels of the core genes were verified by Quantitative Reverse Transcription PCR (qRT-PCR) in other 11 patients and 9 healthy controls. The five core ferroptosis hubgenes were preliminarily identified, and ceRNA network and TF-miRNA-mRNA network were constructed. We identified several pairs of interactions. Finally, verification of qRT-PCR results revealed that CTSB (P=0.001) and HNRNPL (P=0.002) were upregulated, KRAS (P=0.003) and MAP1LC3A (P=0.004) were downregulated in ICAS group, compared with healthy controls. Our results identified four core genes (CTSB, HNRNPL, KRAS and MAP1LC3A) and constructed potential regulatory network, providing the potential therapeutic targets for ICAS.