Dataset Information

Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis.

ABSTRACT: Hypertrophic cardiomyopathy (HCM), the most common heritable cardiomyopathy, is associated with a high risk of sudden cardiac death. The complexity and behavior of the circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) network in HCM have not been thoroughly elucidated. Plasma circRNA and messenger RNA (mRNA) expression profiles were acquired by using a microarray. Weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used to analyze microarray data. Gene modules, consisting of genes with high correlations, were detected and represented by a designated color. The ceRNA network, including circRNA, microRNA (miRNA), and mRNA, was constructed based on the "ceRNA hypothesis" using an integrated systems biology method. By WGCNA, two modules, namely magenta and red modules, were identified as being positively correlated with HCM. In the combined analysis of WGCNA and Limma, 36 hub circRNAs in the magenta module and 83 hub circRNAs in the red module were significantly upregulated compared with the controls. By coexpression analysis, 270 circRNA-mRNA pairs were identified with a coefficient ?0.9 and p < 0.05. With Starbase and miRWalk tools, circRNA-miRNA pairs and miRNA-mRNA pairs were predicted. Once these pairs were combined, the ceRNA network with 6 circRNAs, 29 miRNAs, and 6 mRNAs was constructed. Functional analysis demonstrated that these circRNAs in the ceRNA network were associated with calcium-release channel activity and muscle filament sliding. Our study provided a global perspective and systematic analysis of the circRNA-associated ceRNA network in HCM. The identified circRNAs hsa_circ_0043762, hsa_circ_0036248, and hsa_circ_0071269 may be key regulators involved in HCM pathogenesis.

SUBMITTER: Guo Q

PROVIDER: S-EPMC7399352 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis.

Guo Qi Q Wang Junjie J Sun Runlu R He Zhijian Z Chen Qian Q Liu Wenhao W Wu Maoxiong M Bao Jinlan J Liu Zhaoyu Z Wang Jingfeng J Zhang Yuling Y

Frontiers in genetics 20200728

Hypertrophic cardiomyopathy (HCM), the most common heritable cardiomyopathy, is associated with a high risk of sudden cardiac death. The complexity and behavior of the circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) network in HCM have not been thoroughly elucidated. Plasma circRNA and messenger RNA (mRNA) expression profiles were acquired by using a microarray. Weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used to analyze mic ...[more]

PMID: 32849787

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Project description:BackgroundThe brown adipose tissue (BAT) is a target for treating obesity. BAT losses thermogenic capacity and gains a "white adipose tissue-like" phenotype ("BAT whitening") under thermoneutral environments, which is a potential factor causing a low curative effect in BAT-related obesity treatments. Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNA) to mRNAs and function in various processes by sponging shared microRNAs (miRNAs). However, the roles of circRNA- and lncRNA-related ceRNA networks in regulating BAT whitening remain litter known.ResultsIn this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). MiRNA-seq was performed to investigate miRNA changes during BAT whitening. Then, a combined analysis of circRNA-seq and whole-transcriptome sequencing was used for circRNA assembly and quantification during BAT whitening. Our data showed that 1187 miRNAs and 6204 circRNAs were expressed in the samples, and many of which were identified as significantly changed during BAT whitening. Target prediction showed that D0-selective miRNAs were significantly enriched in the Ras, MAPK, and PI3K-Akt signaling pathways, and Y2-selective miRNAs were predicted to be involved in cell proliferation. The cyclization of several circRNAs could form novel response elements of key thermogenesis miRNAs at the back-splicing junction (BSJ) sites, and in combination with a dual-luciferase reporter assay confirmed the binding between the BSJ site of novel_circ_0013792 and ocu-miR-378-5p. CircRNAs and lncRNAs have high cooperativity in sponging miRNAs during BAT whitening. Both circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA triple networks were significantly involved in immune response-associated biological processes. The D15-selective circRNA might promote BAT whitening by increasing the expression of IDH2. The Y2-selective circRNA-related ceRNA network and lncRNA-related ceRNA network might regulate the formation of the WAT-like phenotype of BAT via MAPK and Ras signaling pathways, respectively.ConclusionsOur work systematically revealed ceRNA networks during BAT whitening in rabbits and might provide new insight into BAT-based obesity treatments.

Project description:BackgroundIntervertebral disc degeneration (IDD) is a leading cause of disability with limited treatment strategies. A better understanding of the mechanism of IDD might enable less invasive and more targeted treatments. This study aimed to identify the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) regulatory mechanisms in IDD. METHODS : The GSE67567 microarray dataset was downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs, miRNAs and mRNAs between IDD and controls were identified. A ceRNA network was constructed on the basis of the interaction between circRNAs and miRNAs, and miRNAs and mRNAs. Pathway enrichment analysis was performed on the mRNAs in the ceRNA network. Then, with 'intervertebral disc degeneration' as keywords, IDD-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were searched for in the Comparative Toxicogenomics Database.ResultsA total of 105 differentially expressed circRNAs, 84 miRNAs and 967 mRNAs were identified. After analysis, 86 circRNA-miRNA, and 126 miRNA-mRNA regulatory relationship pairs were obtained to construct a ceRNA network. The mRNAs were enriched in six KEGG signalling pathways, and four were associated with IDD: the hsa04350: TGF-beta signalling pathway, hsa04068: FoxO signalling pathway, hsa05142: Chagas disease (American trypanosomiasis) and hsa04380: Osteoclast differentiation. An IDD-related ceRNA network was constructed involving four circRNAs, three miRNAs and 11 mRNAs. Auxiliary validation showed that the expression levels of miR-185-5p, miR-486-5p, ACVR1B, FOXO1, SMAD2 and TGFB1 were consistent in different databases.ConclusionsOur study identified some circRNA-miRNA-mRNA interaction axes potentially associated with the progression of IDD, viz.: circRNA_100086-miR-509-3p-MAPK1, circRNA_000200-miR-185-5p-TGFB1, circRNA_104308-miR-185-5p-TGFB1, circRNA_400090-miR-486-5p-FOXO1 and circRNA_400090-miR-486-5p-SMAD2.

Dataset Information

Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis.

Publications

Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis.

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