Identification of key microRNAs and genes associated with abdominal aortic aneurysm based on the gene expression profile.

What is the central question of this study? The aim was to identify abdominal aortic aneurysm (AAA)-associated microRNAs and their target genes in AAA using microarray analysis. What is the main finding and its importance? The main finding was that miR-145 and miR-30c-2* were found to be downregulated microRNAs in AAA, which could exert suppressive effects on AAA progression, and that miR-145 might target RAC2, whereas miR-30c-2* might target PIK3CD, IL1B and RAC2. The findings obtained from the study provide an enhanced understanding of microRNA as a therapeutic target to limit AAA. The aim of the study was to identify abdominal aortic aneurysm (AAA)-associated microRNAs (miRNAs) and genes potentially contributing to AAA. Differential analysis was performed to screen out differentially expressed genes (DEGs) and miRNAs in expression datasets of AAA-related miRNAs [GSE51226 (mouse)] and genes [GSE51227 (mouse) and GSE7084 (human)]. Then, gene ontology (GO) enrichment analysis of DEGs was compared with aneurysm-related GO to screen out DEGs related to the disease. The target genes of differential miRNAs were predicted and used to construct a miRNA-DEG regulatory network, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of target genes. Moreover, the protein-protein interaction network of target genes of miRNAs in the core position (hub-miRNA) with AAA-related genes was constructed to screen out hub genes. Finally, the target relationship between hub-miRNAs and their target genes was verified. There were 20 upregulated miRNAs and 20 downregulated miRNAs in AAA screened from the GSE51226 dataset (mouse). In addition, there were 1154 upregulated genes and 821 downregulated genes in the GSE51227 dataset (mouse), of which 246 DEGs were enriched in aneurysm-related GO entries in AAA. miR-145 and miR-30c-2* were the key miRNAs of AAA, both of which were downregulated in AAA and influenced pathways so as to affect AAA by regulating their respective target genes. The disease-related gene ACTA2 was downregulated, whereas DEGs including PIK3CD, IL1B, RAC2 and SELL were upregulated in AAA. Finally, it was proved that miR-145 targeted RAC2 and SELL, whereas miR-30c-2* targeted PIK3CD, IL1B and RAC2. Taken together, miR-145 and miR-30c-2*, downregulated in AAA, could potentially affect AAA, and miR-145 might target RAC2, whereas miR-30c-2* might target PIK3CD, IL1B and RAC2.

Yang P ，Cai Z ，Wu K ，Hu Y ，Liu L ，Liao M ... -  《-》

miR-30a-GNG2 and miR-15b-ACSS2 Interaction Pairs May Be Potentially Crucial for Development of Abdominal Aortic Aneurysm by Influencing Inflammation.

Gan S ，Pan Y ，Mao J 《-》

Construction of the circRNA-miRNA-mRNA Regulatory Network of an Abdominal Aortic Aneurysm to Explore Its Potential Pathogenesis.

Abdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA. The expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs. The present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p. In conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.

Zhang H ，Bian C ，Tu S ，Yin F ，Guo P ，Zhang J ，Wu Y ，Yin Y ，Guo J ，Han Y ... -  《-》

Identification of key genes and pathways involved in abdominal aortic aneurysm initiation and progression.

Su Z ，Gu Y 《-》

Identification of crucial genes involved in pathogenesis of regional weakening of the aortic wall.

The diameter of the abdominal aortic aneurysm (AAA) is the most commonly used parameter for the prediction of occurrence of AAA rupture. However, the most vulnerable region of the aortic wall may be different from the most dilated region of AAA under pressure. The present study is the first to use weighted gene coexpression network analysis (WGCNA) to detect the coexpressed genes that result in regional weakening of the aortic wall. The GSE165470 raw microarray dataset was used in the present study. Differentially expressed genes (DEGs) were filtered using the "limma" R package. DEGs were assessed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. WGCNA was used to construct the coexpression networks in the samples with regional weakening of the AAA wall and in the control group to detect the gene modules. The hub genes were defined in the significant functional modules, and a hub differentially expressed gene (hDEG) coexpression network was constructed with the highest confidence based on protein-protein interactions (PPIs). Molecular compound detection (MCODE) was used to identify crucial genes in the hDEG coexpression network. Crucial genes in the hDEG coexpression network were validated using the GSE7084 and GSE57691 microarray gene expression datasets. A total of 350 DEGs were identified, including 62 upregulated and 288 downregulated DEGs. The pathways were involved in immune responses, vascular smooth muscle contraction and cell-matrix adhesion of DEGs in the samples with regional weakening in AAA. Antiquewhite3 was the most significant module and was used to identify downregulated hDEGs based on the result of the most significant modules negatively related to the trait of weakened aneurysm walls. Seven crucial genes were identified and validated: ACTG2, CALD1, LMOD1, MYH11, MYL9, MYLK, and TPM2. These crucial genes were associated with the mechanisms of AAA progression. We identified crucial genes that may play a significant role in weakening of the AAA wall and may be potential targets for medical therapies and diagnostic biomarkers. Further studies are required to more comprehensively elucidate the functions of crucial genes in the pathogenesis of regional weakening in AAA.

Zu HL ，Liu HW ，Wang HY 《HEREDITAS》