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

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...

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Autores principales: Osmak, German, Baulina, Natalia, Kiselev, Ivan, Favorova, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701189/
https://www.ncbi.nlm.nih.gov/pubmed/34946964
http://dx.doi.org/10.3390/genes12122016
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author Osmak, German
Baulina, Natalia
Kiselev, Ivan
Favorova, Olga
author_facet Osmak, German
Baulina, Natalia
Kiselev, Ivan
Favorova, Olga
author_sort Osmak, German
collection PubMed
description 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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spelling pubmed-87011892021-12-24 MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis Osmak, German Baulina, Natalia Kiselev, Ivan Favorova, Olga Genes (Basel) Article 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. MDPI 2021-12-18 /pmc/articles/PMC8701189/ /pubmed/34946964 http://dx.doi.org/10.3390/genes12122016 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Osmak, German
Baulina, Natalia
Kiselev, Ivan
Favorova, Olga
MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title_full MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title_fullStr MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title_full_unstemmed MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title_short MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis
title_sort mirna-regulated pathways for hypertrophic cardiomyopathy: network-based approach to insight into pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701189/
https://www.ncbi.nlm.nih.gov/pubmed/34946964
http://dx.doi.org/10.3390/genes12122016
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