ArticleCirculation research2016
Knockdown of Plakophilin 2 Downregulates miR-184 Through CpG Hypermethylation and Suppression of the E2F1 Pathway and Leads to Enhanced Adipogenesis In Vitro.
Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Histone Demethylase KDM5A Is Activated and Pathogenic in a Mouse Model of LMNA-Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Arrhythmogenic Right Ventricular Cardiomyopathy: A Comprehensive Review.Journal of cardiovascular development and disease · 2025Review
- Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study.Life (Basel, Switzerland) · 2025Article
- Epigenetics of cardiomyopathies: the next frontier.Heart failure reviews · 2025Review
- miR-184, a downregulated ovary-elevated miRNA transcriptionally activated by SREBF2, exerts anti-apoptotic properties in ovarian granulosa cells through inducing SMAD3 expression.Cell death & disease · 2024Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Animal Models and Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy Associated with Pathogenic Variants in Intercalated Disc Genes.International journal of molecular sciences · 2024Review
- Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization.Cardiovascular research · 2024Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.Nature communications · 2023Article
- miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLrOxidative medicine and cellular longevity · 2022Article
- The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies.International journal of molecular sciences · 2021Review
- Plakophilin-2 Promotes Lung Adenocarcinoma Development via Enhancing Focal Adhesion and Epithelial-Mesenchymal Transition.Cancer management and research · 2021Article
- Desmosomes as Signaling Hubs in the Regulation of Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- Different Expressions of Pericardial Fluid MicroRNAs in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Ischemic Heart Disease Undergoing Ventricular Tachycardia Ablation.Frontiers in cardiovascular medicine · 2021Article
- The Role of MicroRNAs in Arrhythmogenic Cardiomyopathy: Biomarkers or Innocent Bystanders of Disease Progression?International journal of molecular sciences · 2020Review
- Established and Emerging Mechanisms in the Pathogenesis of Arrhythmogenic Cardiomyopathy: A Multifaceted Disease.International journal of molecular sciences · 2020Review
- Identification of Genes and Pathways Regulated by Lamin A in Heart.Journal of the American Heart Association · 2020Article
- Exercise restores dysregulated gene expression in a mouse model of arrhythmogenic cardiomyopathy.Cardiovascular research · 2020Article
- A microRNA Expression Profile as Non-Invasive Biomarker in a Large Arrhythmogenic Cardiomyopathy Cohort.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationalePKP2, encoding plakophilin 2 (PKP2), is the most common causal gene for arrhythmogenic cardiomyopathy.
objectiveTo characterize miRNA expression profile in PKP2-deficient cells. METHODS AND
resultsControl and PKP2-knockdown HL-1 (HL-1(Pkp2-shRNA)) cells were screened for 750 miRNAs using low-density microfluidic panels. Fifty-nine miRNAs were differentially expressed. MiR-184 was the most downregulated miRNA. Expression of miR-184 in the heart and cardiac myocyte was developmentally downregulated and was low in mature myocytes. MicroRNA-184 was predominantly expressed in cardiac mesenchymal progenitor cells. Knockdown of Pkp2 in cardiac mesenchymal progenitor cells also reduced miR-184 levels. Expression of miR-184 was transcriptionally regulated by the E2F1 pathway, which was suppressed in PKP2-deficient cells. Activation of E2F1, on overexpression of its activator CCND1 (cyclin D1) or knockdown of its inhibitor retinoblastoma 1, partially rescued miR-184 levels. In addition, DNA methyltransferase-1 was recruited to the promoter region of miR-184, and the CpG sites at the upstream region of miR-184 were hypermethylated. Treatment with 5-aza-2'-deoxycytidine, a demethylation agent, and knockdown of DNA methyltransferase-1 partially rescued miR-184 level. Pathway analysis of paired miR-184:mRNA targets identified cell proliferation, differentiation, and death as the main affected biological processes. Knockdown of miR-184 in HL-1 cells and mesenchymal progenitor cells induced and, conversely, its overexpression attenuated adipogenesis.
conclusionsPKP2 deficiency leads to suppression of the E2F1 pathway and hypermethylation of the CpG sites at miR-184 promoter, resulting in downregulation of miR-184 levels. Suppression of miR-184 enhances and its activation attenuates adipogenesis in vitro. Thus, miR-184 contributes to the pathogenesis of adipogenesis in PKP2-deficient cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.