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

Zhang, Hao; Bian, Ce; Tu, Simei; Yin, Fanxing; Guo, Panpan; Zhang, Jian; Wu, Yihao; Yin, Yalin; Guo, Jiahui; Han, Yanshuo

doi:10.1155/2021/9916881

Cited by 12 publications

(7 citation statements)

References 52 publications

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“…Marie et al reported that SELL was associated with the development of AAA ( 59 ). Furthermore, several bioinformatics studies revealed that CCR7 is one of the hub genes of AAA ( 60 , 61 ). Our findings and previous investigations suggest that these genes might be involved in the development of AAA and could be potential biomarkers for AAA, but their diagnostic value needs further validation.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Chen

Ouyang²,

Fang³

et al. 2022

Front. Cardiovasc. Med.

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ObjectivesThe mortality rate of abdominal aortic aneurysm (AAA) is extremely high in the older population. This study aimed to identify potential biomarkers of AAA and aortic rupture and analyze infiltration of immune cells in stable and ruptured AAA samples.MethodsRaw data of GSE47472, GSE57691, and GSE98278 were downloaded. After data processing, the co-expression gene networks were constructed. Gene Ontology and pathway enrichment analysis of AAA- and aortic rupture-related gene modules were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for further enrichment analysis. The CIBERSORT tool was used to analyze the relative abundance of immune cells in samples. Differentially expressed immune-related genes were analyzed between different samples. Predictive models were constructed via extreme gradient boosting, and hub genes were identified according to feature importance.ResultsBlue and yellow modules were significantly related to AAA, and genes in these modules were associated with the aortic wall and immune response, respectively. In terms of aortic rupture, the most relevant module was significantly enriched in the inflammatory response. The results of GSEA and GSVA suggested that immune cells and the inflammatory response were involved in the development of AAA and aortic rupture. There were significant differences in the infiltration of immune cells and expression levels of immune-related genes among different samples. NFKB1 might be an important transcription factor mediating the inflammatory response of AAA and aortic rupture. After the construction of a predictive model, CD19, SELL, and CCR7 were selected as hub genes for AAA whereas OAS3, IFIT1, and IFI44L were identified as hub genes for aortic rupture.ConclusionWeakening of the aortic wall and the immune response both contributed to the development of AAA, and the inflammatory response was closely associated with aortic rupture. The infiltration of immune cells was significantly different between different samples. NFKB1 might be an important transcription factor in AAA and aortic rupture. CD19, SELL, and CCR7 had potential diagnostic value for AAA. OAS3, IFIT1, and IFI44L might be predictive factors for aortic rupture.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Chen

Ouyang²,

Fang³

et al. 2022

Front. Cardiovasc. Med.

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“…Recently, numerous studies have shown that the ceRNA networks regulation, that is the interaction among circRNAs, miRNAs, and mRNAs, was identified to widely exist in various diseases in different species (64)(65)(66). To investigate the ceRNA network and the functions of circRNAs against APEC infection in chicken macrophages, a putative circRNA-miRNA-mRNA network was constructed in current study.…”

Section: Discussionmentioning

confidence: 99%

Analysis of circRNA expression in chicken HD11 cells in response to avian pathogenic E.coli

Sun

Yang

et al. 2022

Front. Vet. Sci.

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Avian pathogenic E. coli (APEC), one of the widespread zoonotic-pathogen, can cause a series of diseases collectively known as colibacillosis. This disease can cause thousands of million dollars economic loss each year in poultry industry and threaten to human health via meat or egg contamination. However, the detailed molecular mechanism underlying APEC infection is still not fully understood. Circular RNAs, a new type of endogenous noncoding RNA, have been demonstrated to involve in various biological processes. However, it is still not clear whether the circRNAs participate in host response against APEC infection. Herein, we utilized the high-throughput sequence technology to identify the circRNA expression profiles in APEC infected HD cells. A total of di erentially expressed (DE) circRNAs were detected in the comparison of APEC infected HD cells vs. wild type HD cells, which were involved in MAPK signaling pathway, Endocytosis, Focal adhesion, mTOR signaling pathway, and VEGF signaling pathway. Specifically, the source genes (BRAF, PPP CB, BCL L , RAB A, and TSC ) and their corresponding DE circRNAs may play a significant role in APEC infection. Moreover, based on ceRNA regulation, we constructed the circRNA-miRNA network and identified a couple of important regulatory relationship pairs related to APEC infection, including circRAB A-gga-miR-b-p, circRAB A-gga-miR-, and circTSC -gga-miR--p. Results indicate that the aforementioned specific circRNAs and circRNA-miRNA network might have important role in regulating host immune response against APEC infection. This study is the first time to investigate the circRNAs expression profile and the biological function of the source genes of the identified DE circRNAs after APEC infection of chicken HD cells. These results would contribute to a better understanding of the molecular mechanisms in host response against APEC infection.

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“…For example, hsa_circ_0087352 was reported to promote the inflammatory response of macrophages in AAA by adsorbing hsa-miR-149-5p ( Murray and Wynn, 2011 ). Three other circRNAs, hsa_circ_0011449, hsa_circ_0081968 and hsa-let-7f-5p , were found to be correlated with the occurrence of AAA by regulating some other inflammatory cytokines, such as SOD2 and CCR7 ( Zhang et al, 2021 ). Recently, the crosstalk between circRNAs and m6A methylation is gradually being revealed.…”

Section: Discussionmentioning

confidence: 99%

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm

Wang

Kan

et al. 2022

Front. Genet.

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Background: N6-methyladenosine (m6A) is the most prevalent non-cap reversible modification present in messenger RNAs and long non-coding RNAs, and its dysregulation has been linked to multiple cardiovascular diseases, including cardiac hypertrophy and atherosclerosis. Although limited studies have suggested that m6A modification contributes to abdominal aortic aneurysm (AAA) development, the full landscape of m6A regulators that mediate modification patterns has not been revealed.Methods: To distinguish the m6A methylation subtypes in AAA patients, an unsupervised clustering method was carried out, based on the mRNA levels of 17 m6A methylation regulators. Differentially expressed genes were identified by comparing clusters. An m6Ascore model was calculated using principal component analysis and structured to assess the m6A methylation patterns of single samples. Subsequently, the relationship between the m6Ascore and immune cells and the hallmark gene set was analyzed. Finally, pairs of circRNA-m6A regulators and m6A regulators-m6A related genes were used to establish a network.Results: We identified three m6A methylation subtypes in the AAA samples. The m6Acluster A and C were characterized as more immunologically activated because of the higher abundance of immune cells than that in m6Acluster B. The m6Acluster B was less enriched in inflammatory pathways and more prevalent in pathways related to extracellular matrix stability. Subsequently, we divided the individual samples into two groups according to the m6Ascore, which suggested that a high m6Ascore predicted more active inflammatory pathways and higher inflammatory cell infiltration. A network consisting of 9 m6A regulators and 37 circRNAs was constructed.Conclusion: This work highlighted that m6A methylation modification was highly correlated with immune infiltration of AAA, which may promote the progression of AAA. We constructed an individualized m6Ascore model to provide evidence for individualized treatments in the future.

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

Cited by 12 publications

References 52 publications

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Analysis of circRNA expression in chicken HD11 cells in response to avian pathogenic E.coli

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm

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