Identification of potential novel biomarkers for abdominal aortic aneurysm based on comprehensive analysis of circRNA‑miRNA‑mRNA networks

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening disorder and, therefore, investigation into its underlying mechanisms in light of the competing endogenous RNAs (ceRNAs) hypothesis has gradually increased. However, there is still lacking systematic analysis on AAA-associated circular RNA (circRNA)-microRNA (miRNA/miR)-messenger RNA (mRNA) interaction networks based on bioinformatics methods. The present study attempted to identify novel molecular biomarkers for AAA by profiling circRNA-miRNA-mRNA networks using three public microarray datasets (GSE7084, GSE57691 and GSE144431). A total of 135 differentially expressed genes (DEGs) and 142 differentially expressed circRNAs were detected using the limma R package with the statistical threshold of P<0.05 and |log 2 fold change (FC)| >1.5.In addition, 12 circRNA-miRNA-mRNA axes were identified to construct upregulated and downregulated ceRNA networks using Cytoscape. Based on molecular complex detection algorithm, (hsa_circ_0057691/0092108/0006845/0082182)-miR-330-5p-calponin 1 (CNN1) and (hsa_circ_0061482/00 11450/0008351/0004121)-miR-326-CD8a molecule (CD8A) were recognized as the center axes in ceRNA networks. Reverse transcription-quantitative PCR results verified the significant downregulation of CNN1 and upregulation of CD8A in human AAA tissues (P<0.05). In addition, four upregulated circRNA/mRNA axes, and five downregulated circRNA/mRNA axes were revealed to have possible biological functions in the pathogenesis of AAA using the Cytoscape software. Receiver operating characteristic analysis demonstrated the accuracy of these nine DEGs involved in these axes for AAA diagnosis with area under the curves >0.80. The present study revealed novel circRNA-miRNA-mRNA networks associated with AAA, especially for CNN1 and CD8A axes with the potential function of 'focal adhesion' and 'immune response', respectively. Overall, the present findings may provide evidence to explore the implicated ceRNAs in the molecular mechanisms and as novel biomarkers for AAA.

Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma

“…After that, we could input the file of the network obtained from the String database into the Cytoscape software [ 20 ], which is widely used for the investigation of genes and gene–gene interactions in cancer research. Moreover, there is a useful and widely used tool (cytohubba) inside the Cytoscape software for identifying the key nodes (genes) in a gene interaction network [ 21 , 22 ] and we applied this tool to identify the top 50 hub genes in the two modules of interest. There are several methods inside the cytohubba tool and we chose the MCC method to identify hub genes, which could be achieved by simple selection on the page of the Cytoscape software.…”

Circulating microRNAs in patients with aneurysmal dilatation of coronary arteries

“…MiRNAs are involved in cardiovascular remodeling, which results in cardiovascular diseases such as CAD, abdominal aortic aneurysm (AAA), and HF ( 16 ). Our understanding the roles of serum miRNAs in patients with CAAD is still not comprehensive; however, essential knowledge came from the studying selected groups of individuals with Kawasaki disease (KD) ( 17-19 ) and AAA ( 20 , 21 ).…”

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

“…AAA is characterized by the infiltration of immune cells, suggesting that the immune system plays a critical role in AAA progression ( 13 , 14 ). However, the ceRNA network and its association with infiltrating immune cells in AAA have not been thoroughly elucidated ( 15 , 16 ).…”