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

Abstract

BackgroundVarious 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.MethodsThe 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.ResultsA 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.ConclusionIn 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.

Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical

“…CircRNAs, as a relatively novel research avenue in AAA, primarily exert their effects through miRNA sponging, possibly achieved through competitive endogenous RNA (ceRNA) mechanisms. Bioinformatics studies have explored potential molecular mechanisms in AAA by constructing ceRNA interaction networks involving circRNAs and miRNAs ( 85 ). For instance, circCBFB acts as a miR-28-5p sponge, promoting the reduction of GRIA4 and LYPD3 levels, thereby decreasing VSMC apoptosis and facilitating AAA progression ( 86 ).…”

Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro

“…circRNAs exert essential biological functions by sponging specific microRNAs (miRNAs), binding RNA-binding proteins, translating proteins, interfering with signalling pathways, and modulating transcription and splicing [ 11 , 12 , 13 , 14 ]. Construction of circRNA-miRNA-messenger RNA (mRNA) networks might help identify new potential diagnostic and therapeutic targets for diseases; for example, circ_0002722-miR-130-PPARG might be associated with the pathogenesis of abdominal aortic aneurysm; this finding thus provides potential therapeutic targets for abdominal aortic aneurysm [ 15 ]. A large number of studies have shown that circRNAs are involved in the occurrence and development of atherosclerosis and may be considered as targets for clinical treatment [ 16 ].…”

Transcription Factor TCF3 Promotes Macrophage-Mediated Inflammation and MMP Secretion in Abdominal Aortic Aneurysm by Regulating miR-143-5p/CCL20

“…12,13 In addition, clinical studies of AAA have shown an increase in the number of M2 macrophages in the lesion area, which is related to the pathologic type of the lesion and the development stage. 14 TCF3, which is an important transcription factor, is known as E2A 15 and has important roles in immune cell differentiation, embryonic development, and cancer. [16][17][18] TCF3 can be expressed in a variety of cells, including embryonic stem cells, mouse cardiomyocytes, 19 liver cancer cells, 20 and macrophages.…”

“…12,13 In addition, clinical studies of AAA have shown an increase in the number of M2 macrophages in the lesion area, which is related to the pathologic type of the lesion and the development stage. 14…”