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

Gan, Shujie; Pan, Yuqin; Mao, Jieqi

doi:10.1089/dna.2019.4994

Cited by 12 publications

(9 citation statements)

References 63 publications

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“…Wang et al thought that UBB, NFIA, sparcl1, and other genes play an important role in AAA by comparing gene expression levels and simply constructing a regulatory network (Wang et al, 2018). Gan et al found that hsa-mir-30a-gng2 and hsa-mir-15b-acss2 may play a role in the development of AAA by screening differentially expressed miRNAs and mRNA and predicting the regulatory relationship through a database (Gan et al, 2019). Gäbel et al (2017) showed that ccl4l1 and ANGPTL4 were closely related to AAA rupture.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the same datasets also showed that chemokines and their ligands were upregulated in AAA and could interact with other factors to play a role in AAA. For example, CCL4L1, CCL3L3, CXCL1, CXCL2, CXCL13, and CCR7 were all highly expressed in AAA (Gäbel et al, 2017;Gan et al, 2019). In one study, GNG2, CXCL1, and CCR7 were considered as central genes in the AAA network, and GNG2 interacted with CXCL1 and CCR7 to participate in the chemokine signaling road (Gan et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…For example, CCL4L1, CCL3L3, CXCL1, CXCL2, CXCL13, and CCR7 were all highly expressed in AAA (Gäbel et al, 2017;Gan et al, 2019). In one study, GNG2, CXCL1, and CCR7 were considered as central genes in the AAA network, and GNG2 interacted with CXCL1 and CCR7 to participate in the chemokine signaling road (Gan et al, 2019). PI3 is an important mediator in the occurrence and development of inflammation and synthesized and secreted by infiltrating neutrophils.…”

Section: Discussionmentioning

confidence: 99%

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Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm

Qiu

Si²,

Zhou

2020

Front. Genet.

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Approximately 13,000 people die of an abdominal aortic aneurysm (AAA) every year. This study aimed to identify the immune response-related genes that play important roles in AAA using bioinformatics approaches. We downloaded the GSE57691 and GSE98278 datasets related to AAA from the Gene Expression Omnibus database, which included 80 AAA and 10 normal vascular samples. CIBERSORT was used to analyze the samples and detect the infiltration of 22 types of immune cells and their differences and correlations. The principal component analysis showed significant differences in the infiltration of immune cells between normal vascular and AAA samples. High proportions of CD4+ T cells, activated mast cells, resting natural killer cells, and 12 other types of immune cells were found in normal vascular tissues, whereas high proportions of macrophages, CD8+ T cells, resting mast cells, and six other types of immune cells were found in AAA tissues. In the selected samples, we identified 39 upregulated (involved in growth factor activity, hormone receptor binding, and cytokine receptor activity) and 133 downregulated genes (involved in T cell activation, cell chemotaxis, and regulation of immune response mediators). The key differentially expressed immune response-related genes were screened using the STRING database and Cytoscape software. Two downregulated genes, PI3 and MAP2K1, and three upregulated genes, SSTR1, GPER1, and CCR10, were identified by constructing a protein–protein interaction network. Functional enrichment of the differentially expressed genes was analyzed, and the expression of the five key genes in AAA samples was verified using quantitative polymerase chain reaction, which revealed that MAP2K1 was downregulated in AAA, whereas SSTR1, GEPR1, and CCR10 were upregulated; there was no significant difference in PI3 expression. Our study shows that normal vascular and AAA samples can be distinguished via the infiltration of immune cells. Five genes, PI3, MAP2K1, SSTR1, GPER1, and CCR10, may play important roles in the development, diagnosis, and treatment of AAA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm

Qiu

Si²,

Zhou

2020

Front. Genet.

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“…Furthermore, our previous bioinformatics prediction analysis revealed that miR-15b-5p may function in the development of AAA by regulating ACSS2 and then affecting the lipid biosynthetic process ( 16 ). PTGS2 (also known as COX-2) is a key regulatory enzyme in lipid metabolism, which was also upregulated in AAA ( 16 ). Thus, it can be hypothesized that PTGS2 may be a downstream target of the miR-15b-5p/ACSS2 interaction.…”

Section: Resultsmentioning

confidence: 99%

“…A previous study from our group integrated the miRNA and mRNA expression profile datasets of aortic samples from patients with AAA and identified several novel miRNA/mRNA interaction pairs that may be crucial in the development of human AAA. These previous results included the predicted interaction pair of miR-15b (which was upregulated in AAA) with the mRNA for acyl-CoA synthetase short chain family member 2 (ACSS2; which was downregulated in AAA) ( 16 ). Therefore, the present study aimed to validate the regulatory relationship between miR-15b and ACSS2 by using a luciferase reporter assay, and to explore their roles in the proliferation and apoptosis of aortic VSMCs by in vitro overexpression or knockdown experiments.…”

Section: Introductionmentioning

confidence: 99%

hsa‑miR‑15b‑5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis

et al. 2021

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A previous bioinformatic analysis from our group predicted that the interaction of microRNA (miRNA/miR)-15b with the acyl-CoA synthetase short chain family member 2 (ACSS2) gene was important for the development of abdominal aortic aneurysm (AAA). Apoptosis of aortic vascular smooth muscle cells (VSMCs) is a pathological feature of AAA. The present study aimed to explain the roles of miR-15b/ACSS2 in AAA by exploring their effects on the proliferation and apoptosis of aortic VSMCs. Human aortic VSMCs (T/G HA-VSMC cell line) were divided into six groups and were transfected with miR-15b-5p mimics, mimic negative control (NC), miR-15b-5p inhibitors, inhibitor NC, miR-15b-5p mimics+pcDNA3.1 and miR-15b-5p mimics+ACSS2-overexpessing vector. CCK-8 assay was used to determine cell proliferation. Annexin V-FITC/PI staining and flow cytometry assays were used to measure cell apoptosis. Dual-luciferase reporter assays were used to confirm the targeted relationship between miR-15b-5p and ACSS2. Reverse transcription-quantitative PCR and/or western blotting were used to examine the expression levels of miR-15b-5p, ACSS2 and prostaglandin-endoperoxide synthase 2 (PTGS2). Following transfection of T/G HA-VSMCs with mimics and inhibitors to respectively upregulate and downregulate miR-15b-5p, the results demonstrated that overexpression of miR-15b-5p inhibited cell proliferation and promoted cell apoptosis; silencing of miR-15b-5p obtained the opposite results. ACSS2 may be a direct target of miR-15b-5p, since the luciferase activity of a ACSS2 wild-type vector, but not that of a ACSS2 mutant reporter, was significantly inhibited by miR-15b-5p mimics compared with controls. Additionally, the expression levels of ACSS2 and its downstream gene PTGS2 were significantly reduced or increased following transfection with miR-15b-5p mimics or inhibitors, respectively. Furthermore, overexpression of ACSS2 reversed the antiproliferative and proapoptotic effects of miR-15b-5p mimics by blocking the production of PTGS2 protein. In conclusion, miR-15b-5p may promote the apoptosis and inhibit the proliferation of aortic VSMCs via targeting the ACSS2/PTGS2 axis. The present study provided preliminary evidence indicating that the miR-15b-5p/ACSS2/PTGS2 axis may be a potential target for the treatment of AAA.

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Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis

Huang,

Shi,

Huang

et al. 2024

Biochem Genet

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

Cited by 12 publications

References 63 publications

Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm

Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm

hsa‑miR‑15b‑5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis

Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis

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