Integrated Analysis of circRNA-miRNA-mRNA ceRNA Network in Cardiac Hypertrophy

Chen, Yanghao; Zhong, Lingfeng; Xia, Hong; Zhu, Qianli; Wang, Song-Jie; Han, Jibo; Huang, Weiping; Ye, Bozhi

doi:10.3389/fgene.2022.781676

Cited by 7 publications

(6 citation statements)

References 53 publications

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“…In another study on animal models of myocardial hypertrophy, 3 mRNA, 4 miRNAs, and 4 circRNAs were found to play an important role in myocardial hypertrophy. Bioinformatics methods were used for the study [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

et al. 2023

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Background Hypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated. Materials and methods By analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model. Results Three large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM. Conclusion In this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM.

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Section: Discussionmentioning

confidence: 99%

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

et al. 2023

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“…Three studies have recently analyzed the ceRNA network in cardiac hypertrophy/cardiac fibrosis/heart failure ( Gu et al, 2020 ; Chen et al, 2022 ; Li et al, 2022 ). Li et al demonstrated distinct pathological features in the three stages of heart failure and constructed a ceRNA regulatory network in cardiac remodeling and dysfunction ( Li et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…In our study, we had more replicates per group (n = 5), and whole transcriptome RNA-seq was used. Chen et al used data from human iPSC-derived cardiomyocytes from public databases ( Aggarwal et al, 2014 ) and established a circRNA-mediated ceRNA regulatory network in cardiac hypertrophy ( Chen et al, 2022 ), which may not be representative of specific physiopathological features during cardiac hypertrophy. Gu et al determined the circRNA expression profile and conducted constructed a ceRNA network in TGF-β1-treated mouse cardiac fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis

et al. 2022

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Cardiac hypertrophy initially serves as an adaptive response to physiological and pathological stimuli. Sustained hypertrophy progress to pathological cardiac hypertrophy, cardiac fibrosis and ultimately lead to heart failure, one of the leading medical causes of mortality worldwide. Intervention of pathological cardiac hypertrophy can effectively reduce the occurrence of heart failure. Abundant factors, such as adrenergic, angiotensin, and endothelin (ET-1) receptors, have been shown to participate in the regulation of pathological cardiac hypertrophy. Recently, an increasing number of studies have indicated that circRNA and circRNA-miRNA–mRNA network regulation is indispensable for the posttranscriptional regulation of mRNA in cardiac hypertrophy. In our study, the morphological, cardiac function and pathological changes during cardiac hypertrophy were investigated. RNA sequencing identified 93 circRNAs that were differentially expressed in the TAC_2w group, and 55 circRNAs in the TAC_4w group compared with the sham group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified several significant pathways, including hypertrophic cardiomyopathy, extracellular matrix (ECM)-receptor interaction and focal adhesion. Coexpression analyses were performed for differentially expressed circRNAs and differentially expressed mRNAs. Based on gene set enrichment analysis (GSEA), 8 circRNAs (mmu-Nfkb1_0001, mmu-Smad4_0007, mmu-Hecw2_0009, mmu-Itgbl1_0002, mmu-Lrrc2_0005, mmu-Cpeb3_0007, mmu-Ryr2_0040, and mmu-Rtn4_0001) involved in cardiac hypertrophy and cardiac fibrosis were identified. We validated some key circRNAs by qPCR. The crucial coexpression of circRNA–mRNA and its interaction with miRNA showed the possible mechanism of circRNAs in the process of cardiac dysfunction. Our results may provide promising targets for the treatment of pathological cardiac hypertrophy and fibrosis.

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“…In addition, the plug-in can calculate the information of each node in the network diagram. According to recent research studies, the top 25% of nodes in the ceRNA network can be selected [26], and only the complete circRNA-miRNA-mRNA axes were retained.…”

Section: Reconstruction Of the Key Circrna-mirna-mrnamentioning

confidence: 99%

Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis

Chen

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.

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Integrated Analysis of circRNA-miRNA-mRNA ceRNA Network in Cardiac Hypertrophy

Cited by 7 publications

References 53 publications

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis

Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis

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