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MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With...

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Autores principales: Ágg, Bence, Baranyai, Tamás, Makkos, András, Vető, Borbála, Faragó, Nóra, Zvara, Ágnes, Giricz, Zoltán, Veres, Dániel V., Csermely, Péter, Arányi, Tamás, Puskás, László G., Varga, Zoltán V., Ferdinandy, Péter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031673/
https://www.ncbi.nlm.nih.gov/pubmed/29973623
http://dx.doi.org/10.1038/s41598-018-27740-3
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author Ágg, Bence
Baranyai, Tamás
Makkos, András
Vető, Borbála
Faragó, Nóra
Zvara, Ágnes
Giricz, Zoltán
Veres, Dániel V.
Csermely, Péter
Arányi, Tamás
Puskás, László G.
Varga, Zoltán V.
Ferdinandy, Péter
author_facet Ágg, Bence
Baranyai, Tamás
Makkos, András
Vető, Borbála
Faragó, Nóra
Zvara, Ágnes
Giricz, Zoltán
Veres, Dániel V.
Csermely, Péter
Arányi, Tamás
Puskás, László G.
Varga, Zoltán V.
Ferdinandy, Péter
author_sort Ágg, Bence
collection PubMed
description Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart.
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spelling pubmed-60316732018-07-12 MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium Ágg, Bence Baranyai, Tamás Makkos, András Vető, Borbála Faragó, Nóra Zvara, Ágnes Giricz, Zoltán Veres, Dániel V. Csermely, Péter Arányi, Tamás Puskás, László G. Varga, Zoltán V. Ferdinandy, Péter Sci Rep Article Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart. Nature Publishing Group UK 2018-07-04 /pmc/articles/PMC6031673/ /pubmed/29973623 http://dx.doi.org/10.1038/s41598-018-27740-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ágg, Bence
Baranyai, Tamás
Makkos, András
Vető, Borbála
Faragó, Nóra
Zvara, Ágnes
Giricz, Zoltán
Veres, Dániel V.
Csermely, Péter
Arányi, Tamás
Puskás, László G.
Varga, Zoltán V.
Ferdinandy, Péter
MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title_full MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title_fullStr MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title_full_unstemmed MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title_short MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
title_sort microrna interactome analysis predicts post-transcriptional regulation of adrb2 and ppp3r1 in the hypercholesterolemic myocardium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031673/
https://www.ncbi.nlm.nih.gov/pubmed/29973623
http://dx.doi.org/10.1038/s41598-018-27740-3
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