Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm

Liang Chen; Shuangshuang Wang; Zheyu Wang; Yuting Liu; Yi Xu; Shuofei Yang; Guanhua Xue

doi:10.3389/fcvm.2022.955838

Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm

Front Cardiovasc Med. 2022 Aug 4:9:955838. doi: 10.3389/fcvm.2022.955838. eCollection 2022.

Authors

Liang Chen¹, Shuangshuang Wang², Zheyu Wang¹, Yuting Liu¹, Yi Xu¹, Shuofei Yang¹, Guanhua Xue¹

Affiliations

¹ Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Songyuan Central Hospital, Songyuan Children's Hospital, Songyuan, China.

Abstract

Background: Various studies have highlighted the role of circular RNAs (circRNAs) as critical molecular regulators in cardiovascular diseases, but its role in abdominal aortic aneurysm (AAA) is unclear. This study explores the potential molecular mechanisms of AAA based on the circRNA-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) network and immune cell infiltration patterns.

Methods: The expression profiles of circRNAs (GSE144431) and mRNAs (GSE57691 and GSE47472) were obtained from the Gene Expression Omnibus (GEO). Then, the differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) between AAA patients and healthy control samples, and the target miRNAs of these DEmRNAs and DEcircRNAs were identified. Based on the miRNA-DEmRNAs and miRNA-DEcircRNAs pairs, the ceRNA network was constructed. Furthermore, the proportion of the 22 immune cell types in AAA patients was assessed using cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. The expressions of key genes and immune cell infiltration were validated using clinical specimens.

Results: A total of 214 DEmRNAs were identified in the GSE57691 and GSE47472 datasets, and 517 DEcircRNAs were identified in the GSE144431 dataset. The ceRNA network included 19 circRNAs, 36 mRNAs, and 68 miRNAs. Two key genes, PPARG and FOXO1, were identified among the hub genes of the established protein-protein interaction between mRNAs in the ceRNA network. Moreover, seven types of immune cells were differentially expressed between AAA patients and healthy control samples. Hub genes in ceRNA, such as FOXO1, HSPA8, and RAB5C, positively correlated with resting CD4 memory T cells or M1 macrophages, or both.

Conclusion: In conclusion, a ceRNA interaction axis was constructed. The composition of infiltrating immune cells was analyzed in the abdominal aorta of AAA patients and healthy control samples. This may help identify potential therapeutic targets for AAA.

Keywords: abdominal aortic aneurysm; bioinformatic analysis; circular RNA; competing endogenous RNA network; immune cell infiltration.