Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm
Open Access
- 4 August 2022
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cardiovascular Medicine
- Vol. 9, 955838
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
Funding Information
- National Natural Science Foundation of China
This publication has 61 references indexed in Scilit:
- miRmap: Comprehensive prediction of microRNA target repression strengthNucleic Acids Research, 2012
- Tissue‐ and Plasma‐Specific MicroRNA Signatures for Atherosclerotic Abdominal Aortic AneurysmJournal of the American Heart Association, 2012
- miRcode: a map of putative microRNA target sites in the long non-coding transcriptomeBioinformatics, 2012
- Tumor necrosis factor-α regulates p27kip expression and apoptosis in smooth muscle cells of human carotid plaques via forkhead transcription factor O1Experimental and Molecular Pathology, 2011
- Pathophysiology and epidemiology of abdominal aortic aneurysmsNature Reviews Cardiology, 2010
- Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysmAtherosclerosis, 2010
- Association of PPARγ allelic variation, osteoprotegerin and abdominal aortic aneurysmClinical Endocrinology, 2009
- Dominant-Negative Loss of PPARγ Function Enhances Smooth Muscle Cell Proliferation, Migration, and Vascular RemodelingArteriosclerosis, Thrombosis, and Vascular Biology, 2009
- Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and HypertensionCell Metabolism, 2008
- FOXO1 Functions as a Master Switch That Regulates Gene Expression Necessary for Tumor Necrosis Factor-induced Fibroblast ApoptosisJournal of Biological Chemistry, 2005