Identification of novel hub gene and biological pathways associated with ferroptosis in In-Stent Restenosis

Published: 20 January 2025| Version 1 | DOI: 10.17632/5cvxh9r4kc.1
Contributors:
Shan Jin, Meixia Zhang, Lingli Xu, Wenping Cai, Xia Zhao, Jin Du, Jin Qiu, Huiling Xu, Siming Huang, Yunmiao Guo, Lin Tao, Lijuan Pang

Description

The current study aims to reveal the molecular targets for neointimal hyperplasia through integrated analysis of data from gene expression omnibus (GEO) databases and single-cell sequencing (scRNA-Seq). The gene expression data used for the study and analysis were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/). The GSE46560 dataset included mRNA sequencing data from 11 restenosis human samples and 11 non-restenosis human samples of blood. The GSE60959 dataset included mircoRNA (miRNA) sequencing data from 10 plasma samples of patients with ISR. The GSE182225 dataset included lncRNA sequencing data from serum samples of 3 restenosis patients and 3 non-restenosis donors. The list of ferroptosis related genes was obtained from Ferr Db V2 database (http://www.zhounan.org/ferrdb/current/). Using a rat carotid artery balloon injury model to simulate restenosis after PCI. The common carotid arteries were collected for single-cell sequencing. We screened ten common differentially expressed genes (Co-DEGs) including BID, SP1, NCF2, HERPUD1, RICTOR, LAMP2, CAT, ACSL1, CS, and ANO6 from the GEO and FerrDb V2. GO/KEGG analyses indicated that metabolic reactions, particularly glyoxylate and dicarboxylate metabolism pathways, are the main molecular events. Immune infiltration analysis showed significant correlations between the expression of Co-DEGs and the infiltration of macrophages, dendritic cells, eosinophils, and neutrophils. Moreover, we identified SP1 as a potential therapeutic target associated with ferroptosis in ISR and constructed a lncRNA-miRNA-SP1 regulatory network. Using scRNA-Seq data to validate the expression of Co-DEGs in the neointima, we found that metabolic pathways such as carbon metabolism, peroxisomes, and reactive oxygen species were enriched. Immune infiltration examined the relationship between Co-DEGs and immune cells, revealing negative correlation between SP1 and neutrophils, and positive correlation between BID and macrophages.

Files

Institutions

Shihezi University

Categories

Genomics

Licence