M-class hypertrophic cardiomyopathy cardiac actin mutations increase calcium sensitivity of regulated thin filaments

Teng, Grace Zi; Shaikh, Zeeshan; Liu, Haidun; Dawson, John F.

doi:10.1016/j.bbrc.2019.08.151

Cited by 9 publications

(4 citation statements)

References 22 publications

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“…Additionally, KEGG research demonstrated that it may be associated with gap junctions, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, and regulation of the actin cytoskeleton. These mechanisms are similar to the calcium release channel activity described previously [44][45][46][47][48]. This strongly suggests that the circRNAs found in the ceRNA network may play an essential role in the etiology of HCM.…”

Section: Plos Onesupporting

confidence: 85%

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: Plos Onesupporting

confidence: 85%

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

et al. 2023

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“…One of our aims is to understand how changes in the cardiac actin gene (ACTC) lead to different cardiomyopathies. We have conducted molecular-level studies on several ACTC variants [5][6][7][8][9], however, our ultimate goal is to integrate our molecular knowledge of ACTC biochemical changes with physiological dysfunction by editing the cardiac actin gene in an animal model.…”

Section: Introductionmentioning

confidence: 99%

Zebrafishacta1bas a Candidate for Modeling Human Actin Cardiomyopathies

Prill,

Ojehomon,

Sandhu

et al. 2023

Preprint

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Heart failure is the leading cause of mortality worldwide, primarily associated with cardiovascular disease. Many heart muscle diseases are caused by mutations in genes that encode contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modelling cardiac diseases due to their ability to develop without a functional heart throughout embryonic development. However, genome duplication in the teleost lineage poses a unique challenge by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart:acta1b, actc2, and duplicates ofactc1aon chromosomes 19 and 20. In this study, we characterize the actin genes involved in early zebrafish heart development usingin situhybridization and CRISPR targeting to determine the most suitable gene for modelling actin changes observed in human patients with heart disease. Theactc1aandacta1bgenes are predominantly expressed during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPR. Considering the duplication of theactc1agene, we recommendacta1bas the best gene for targeted cardiac actin research.

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“…We seek to understand how changes in the cardiac actin gene (ACTC) in people lead to different cardiomyopathies. We have studied several ACTC variants at the molecular level [5][6][7][8][9] ; however, our goal is to integrate our molecular knowledge of ACTC biochemical changes with physiological dysfunction in a whole animal by gene editing the cardiac actin gene in the model organism.…”

Section: Introductionmentioning

confidence: 99%

Which actin genes are necessary for zebrafish heart development and function?

Prill

Ojehomon

Sandhu

et al. 2020

Preprint

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Heart failure is the number one cause of mortality in the world, contributed to by cardiovascular disease. Many diseases of the heart muscle are caused by mutations in genes encoding contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modeling cardiac disease since embryos can develop without a functional heart. However, genome duplication in the teleost lineage creates a unique obstacle by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart: acta1b; actc1c; and duplicates of actc1a on chromosome 19 and 20. Here, we characterize the actin genes involved in early zebrafish heart development using in situ hybridization and CRISPR targeting to determine which gene is best to model changes seen in human patients with heart disease. The actc1a and acta1b genes are predominant during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPRs. Targeting these two cardiac genes with CRISPRs simultaneously results in a more severe phenotype than their individual counterparts, with the results suggesting compensation for lost actin genes by other actin paralogues. Given the duplication of the actc1a gene, we recommend acta1b as the best gene for targeted cardiac actin research.

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M-class hypertrophic cardiomyopathy cardiac actin mutations increase calcium sensitivity of regulated thin filaments

Cited by 9 publications

References 22 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

Zebrafishacta1bas a Candidate for Modeling Human Actin Cardiomyopathies

Which actin genes are necessary for zebrafish heart development and function?

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