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

Abstract 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 validati...

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Autores principales:	Bence Ágg, Tamás Baranyai, András Makkos, Borbála Vető, Nóra Faragó, Ágnes Zvara, Zoltán Giricz, Dániel V. Veres, Péter Csermely, Tamás Arányi, László G. Puskás, Zoltán V. Varga, Péter Ferdinandy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13fda4bbf4064b339b6972ee7ccd3d94
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spelling	oai:doaj.org-article:13fda4bbf4064b339b6972ee7ccd3d942021-12-02T11:40:45ZMicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium10.1038/s41598-018-27740-32045-2322https://doaj.org/article/13fda4bbf4064b339b6972ee7ccd3d942018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27740-3https://doaj.org/toc/2045-2322Abstract 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.Bence ÁggTamás BaranyaiAndrás MakkosBorbála VetőNóra FaragóÁgnes ZvaraZoltán GiriczDániel V. VeresPéter CsermelyTamás ArányiLászló G. PuskásZoltán V. VargaPéter FerdinandyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
description	Abstract 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.
format	article
author	Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy
author_facet	Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy
author_sort	Bence Ágg
title	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_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_sort	microrna interactome analysis predicts post-transcriptional regulation of adrb2 and ppp3r1 in the hypercholesterolemic myocardium
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/13fda4bbf4064b339b6972ee7ccd3d94
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MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

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