Identification of Circ-FNDC3B, an Overexpressed circRNA in Abdominal Aortic Aneurysm, as a Regulator of Vascular Smooth Muscle Cells

Liu, Yiming; Zhong, Zhisheng; Xiao, Liying; Li, Wendong; Wang, Zhong; Duan, Zongkui; Li, Xiaoqiang

doi:10.1536/ihj.21-186

Cited by 15 publications

(3 citation statements)

References 32 publications

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“…Third, MultiSuSiE fine-mapped a conserved variant, rs4894803, at the FNDC3B locus for resting heart rate (Figure 6d and Supplementary Table 13). FNDC3B codes for a circular RNA transcript, circ-FNDC3B, in addition to its regular protein product; circ-FNDC3B is involved in multiple aspects of cardiovascular physiology including cardiomyocte apoptosis 64 , blood vessel formation 64 , and regulation of ADAM10, a gene whose overexpression is related to aortic aneurysm 65 . rs4894803 was not fine-mapped using Afr47k, Eur47k, or Eur94k; failure to fine-map rs4894803 using Afr47k was due to lower MAF (0.14 in Afr47k vs 0.42 in Eur47k), and failure to fine-map rs4894803 using Eur47k and Eur94k was due to high levels of LD (LD 4 th moment = 24 in Eur47k vs 6.1 in Afr47k).…”

Section: Resultsmentioning

confidence: 99%

MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data

Rossen,

Shi,

Strober

et al. 2024

Preprint

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Leveraging data from multiple ancestries can greatly improve fine-mapping power due to differences in linkage disequilibrium and allele frequencies. We propose MultiSuSiE, an extension of the sum of single effects model (SuSiE) to multiple ancestries that allows causal effect sizes to vary across ancestries based on a multivariate normal prior informed by empirical data. We evaluated MultiSuSiE via simulations and analyses of 14 quantitative traits leveraging whole-genome sequencing data in 47k African-ancestry and 94k European-ancestry individuals from All of Us. In simulations, MultiSuSiE applied to Afr47k+Eur47k was well-calibrated and attained higher power than SuSiE applied to Eur94k; interestingly, higher causal variant PIPs in Afr47k compared to Eur47k were entirely explained by differences in the extent of LD quantified by LD 4th moments. Compared to very recently proposed multi-ancestry fine-mapping methods, MultiSuSiE attained higher power and/or much lower computational costs, making the analysis of large-scale All of Us data feasible. In real trait analyses, MultiSuSiE applied to Afr47k+Eur94k identified 579 fine-mapped variants with PIP > 0.5, and MultiSuSiE applied to Afr47k+Eur47k identified 44% more fine-mapped variants with PIP > 0.5 than SuSiE applied to Eur94k. We validated MultiSuSiE results for real traits via functional enrichment of fine-mapped variants. We highlight several examples where MultiSuSiE implicates well-studied or biologically plausible fine-mapped variants that were not implicated by other methods.

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Section: Resultsmentioning

confidence: 99%

MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data

Rossen,

Shi,

Strober

et al. 2024

Preprint

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“…Liu et al. demonstrated that circFNDC3B expression was elevated in aortic tissue of AAA patients ( 106 ). They further isolated and cultured primary VSMCs from AAA patients and found that the expression of circFNDC3B was higher in them and angiotensin II (Ang-II) induced circFNDC3B expression in a dose-dependent manner.…”

Section: The Roles Of Circfndc3b In Other Diseasesmentioning

confidence: 99%

Emerging landscape of circFNDC3B and its role in human malignancies

et al. 2023

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In recent years, more attention has been paid to expanding the abundance of Circular RNAs (circRNAs), while the circRNAs that have been found to have significant functions have not been studied in different diseases. CircFNDC3B is one of the most researched circRNAs generated from fibronectin type III domain-containing protein 3B (FNDC3B) gene. Accumulating researches have reported the multiple functions of circFNDC3B in different cancer types and other non-neoplastic diseases, and predicted that circFNDC3B might be a potential biomarker. Notably, circFNDC3B can play roles in different diseases by binding to various microRNAs (miRNAs), binding to RNA-binding proteins (RBPs), or encoding functional peptides. This paper systematically summarizes the biogenesis and function of circRNAs, reviews and discusses the roles and molecular mechanisms of circFNDC3B and its target genes in different cancers and non-neoplastic diseases, which will do favor to broaden our comprehension of the function of circRNAs and facilitate subsequent research on circFNDC3B.

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“…The main pathological features of AAA include smooth muscle cell (SMC) dysfunction, inflammation, immune cell infiltration, and extracellular matrix remodeling ( 8 ). Studies have shown an association between circ-FNDC3B and angiotensin II (Ang II) induced SMC dysfunction, suggesting that circ-FNDC3B/miR-143-3p/ADAM10 axis may regulate AAA pathogenesis ( 9 ). Further investigation of circ-Sirt1/miR-132/212/SIRT1 in SMC phenotypic switching provided another perspective on the pathogenesis of AAA ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Wang²,

Wang³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundVarious 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.MethodsThe 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.ResultsA 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.ConclusionIn 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.

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Identification of Circ-FNDC3B, an Overexpressed circRNA in Abdominal Aortic Aneurysm, as a Regulator of Vascular Smooth Muscle Cells

Cited by 15 publications

References 32 publications

MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data

MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data

Emerging landscape of circFNDC3B and its role in human malignancies

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

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