Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation

Qingwen Meng; Yiqian Xu; Xuebin Ling; Huajiang Liu; Shun Ding; Haolin Wu; Dongming Yan; Xingyue Fang; Tianfa Li; Qibing Liu

doi:10.1186/s12872-022-02747-x

Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation

BMC Cardiovasc Disord. 2022 Jul 29;22(1):339. doi: 10.1186/s12872-022-02747-x.

Authors

Qingwen Meng^#^{1

2}, Yiqian Xu^#³, Xuebin Ling^#¹, Huajiang Liu¹, Shun Ding³, Haolin Wu³, Dongming Yan³, Xingyue Fang¹, Tianfa Li⁴, Qibing Liu^{5

6}

Affiliations

¹ Deparment of Cardiology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, China.
² Hainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan Medical University, Haikou, 570100, China.
³ Department of Pharmacology, Hainan Medical University, Haikou, 570100, China.
⁴ Deparment of Cardiology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, China. 2223084306@qq.com.
⁵ Department of Pharmacology, Hainan Medical University, Haikou, 570100, China. qibing.liu@hainmc.edu.cn.
⁶ Department of Pharmacy, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, China. qibing.liu@hainmc.edu.cn.

^# Contributed equally.

Abstract

Background: Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun".

Methods: First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins.

Results: Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group.

Conclusions: Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.

Keywords: Bioinformatics analysis; Coronary atherosclerosis; Ferroptosis; Overlapping genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Computational Biology / methods
Coronary Artery Disease* / genetics
Ferroptosis* / genetics
Humans
Mice
Proliferating Cell Nuclear Antigen

Substances

Proliferating Cell Nuclear Antigen