MicroRNAs in Hypertrophic, Arrhythmogenic and Dilated Cardiomyopathy

Chiti, Enrica; Paolo, Marco Di; Turillazzi, Emanuela; Rocchi, Anna

doi:10.3390/diagnostics11091720

Cited by 19 publications

(19 citation statements)

References 133 publications

(187 reference statements)

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“…For the rest of the miRNAs, the number of the key genes is significantly less than the size of their LCCs. It can be noted that the greatest number of targets (16%) were identified as key genes for hsa-miR-451, regulating the smallest number of genes; for the rest of the miRNAs, the algorithm proposed in [ 11 ] allowed us to narrow down the number of analyzed targets (key genes) to less than or equal to 6% of its total number.…”

Section: Resultsmentioning

confidence: 99%

“…As a result, miRNAs are implicated in the fine regulation of a diverse spectrum of physiological processes; miRNAs’ dysregulation is associated with many pathological processes in humans, including hypertrophy, fibrosis, and apoptosis of myocardial cells [ 6 , 7 ]. miRNAs have been shown to be involved in the development of various cardiovascular diseases, such as atherosclerosis, myocardial ischemia, and heart failure (reviewed in [ 8 , 9 , 10 , 11 , 12 ]).…”

Section: Introductionmentioning

confidence: 99%

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MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis

Osmak

Baulina

Kiselev

et al. 2021

Genes

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Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease. The wide spread of high-throughput sequencing casts doubt on its monogenic nature, suggesting the presence of mechanisms of HCM development independent from mutations in sarcomeric genes. From this point of view, HCM may arise from the interactions of several HCM-associated genes, and from disturbance of regulation of their expression. We developed a bioinformatic workflow to study the involvement of signaling pathways in HCM development through analyzing data on human heart-specific gene expression, miRNA-target gene interactions, and protein–protein interactions, available in open databases. Genes regulated by a pool of miRNAs contributing to human cardiac hypertrophy, namely hsa-miR-1-3p, hsa-miR-19b-3p, hsa-miR-21-5p, hsa-miR-29a-3p, hsa-miR-93-5p, hsa-miR-133a-3p, hsa-miR-155-5p, hsa-miR-199a-3p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-451a, and hsa-miR-497-5p, were considered. As a result, we pinpointed a module of TGFβ-mediated SMAD signaling pathways, enriched by targets of the selected miRNAs, that may contribute to the cardiac remodeling in HCM. We suggest that the developed network-based approach could be useful in providing a more accurate glimpse on pathological processes in the disease pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis

Osmak

Baulina

Kiselev

et al. 2021

Genes

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“…The predicted miRNA–mRNA pairs identified in our study offer biological guidance for investigating this gene expression regulatory system in the context of cardiac development and disease associations. The experimental system utilizing isoprenaline stimulation readily identified miRNAs reported to be upregulated in HCM and heart failure patients as well as in studies of cardiac hypertrophic growth ( Figure 6 ) [ 46 , 47 ]. Even though the importance of altered miRNA levels and the resulting deregulation of gene expression in the development of CVD pathology is known, there are still many gaps in our knowledge.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating miRNAs are currently studied as potential biomarkers in various CVDs by characterizing specific miRNA blood profiles [ 50 ]. Particularly, miR-21 has consistently been reported as circulating in the blood of HCM patients at elevated concentrations, making it an interesting biomarker target ( Figure 6 ) (reviewed in [ 46 ]). Nevertheless, the biomarker aspect of miRNAs is still in the early development stage.…”

Section: Discussionmentioning

confidence: 99%

New Tricks with Old Dogs: Computational Identification and Experimental Validation of New miRNA–mRNA Regulation in hiPSC-CMs

et al. 2022

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Cardiovascular disease is still the leading cause of morbidity and mortality worldwide. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a valuable widespread in vitro model to study cardiac disease. Herein, we employ the hiPSC-CM model to identify novel miRNA–mRNA interaction partners during cardiac differentiation and β-adrenergic stress. Whole transcriptome and small RNA sequencing data were combined to identify novel miRNA–mRNA interactions. Briefly, mRNA and miRNA expression profiles were integrated with miRNA target predictions to identify significant statistical dependencies between a miRNA and its candidate target set. We show by experimental validation that our approach discriminates true from false miRNA target predictions. Thereby, we identified several differentially expressed miRNAs and focused on the two top candidates: miR-99a-5p in the context of cardiac differentiation and miR-212-3p in the context of β-adrenergic stress. We validated some target mRNA candidates by 3′ UTR luciferase assays as well as in transfection experiments in the hiPSC-CM model system. Our data show that iPSC-derived cardiomyocytes and computational modeling can be used to uncover new valid miRNA–mRNA interactions beyond current knowledge.

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“…MiRNAs have attracted the attention of researchers in various fields [ 38 , 39 , 40 , 41 ]. They influence many signaling pathways involved in inflammation [ 42 , 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

MiRNAs as New Tools in Lesion Vitality Evaluation: A Systematic Review and Their Forensic Applications

et al. 2021

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Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and tissue alterations at the histological examination, all of which are supposedly present in antemortem rather than post-mortem wounds. Nevertheless, some doubts about the reliability of those markers have arisen. Furthermore, the lack of a standardized protocol and the operator dependency of this approach make the proper interpretation of its results difficult. Moreover, a differential miRNAs expression has been demonstrated in antemortem and post-mortem wounds. Herein, a systematic review concerning the current knowledge about the use of miRNAs in lesion vitality evaluation is carried out, to encourage researchers to deepen this peculiar study area. A compendium about the potential miRNAs that may be further investigated as vitality markers is also provided. The aim is to collect all available data about this topic to direct further studies on this field and highlight the future applications of miRNAs in forensic pathology. We found 20 articles and a total of 51 miRNAs that are involved in inflammation and wound healing. Further studies are certainly needed to deepen the role of miRNAs in inflammatory processes in lesioned skin and to evaluate their reliability in distinguishing between antemortem and post-mortem lesions.

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MicroRNAs in Hypertrophic, Arrhythmogenic and Dilated Cardiomyopathy

Cited by 19 publications

References 133 publications

MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis

MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis

New Tricks with Old Dogs: Computational Identification and Experimental Validation of New miRNA–mRNA Regulation in hiPSC-CMs

MiRNAs as New Tools in Lesion Vitality Evaluation: A Systematic Review and Their Forensic Applications

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