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

Bence Ágg, Tamás Baranyai, András Makkos, Borbála Veto, Nóra Faragó, A. Zvara, Z. Giricz, Dániel V. Veres, P. Csermely, T. Arányi, L. Puskás, Zoltán V. Varga, Péter Ferdinandy

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemiainduced 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.

Original languageEnglish
Article number10134
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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MicroRNAs
Myocardium
Messenger RNA
Hypercholesterolemia
Down-Regulation
Adrenergic beta-2 Receptors
Calcium-Calmodulin-Dependent Protein Kinases
Gene Ontology
Proteins
Calcineurin
Protein-Serine-Threonine Kinases
Luciferases
Western Blotting
Polymerase Chain Reaction

ASJC Scopus subject areas

  • General

Cite this

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium. / Ágg, Bence; Baranyai, Tamás; Makkos, András; Veto, Borbála; Faragó, Nóra; Zvara, A.; Giricz, Z.; Veres, Dániel V.; Csermely, P.; Arányi, T.; Puskás, L.; Varga, Zoltán V.; Ferdinandy, Péter.

In: Scientific Reports, Vol. 8, No. 1, 10134, 01.12.2018.

Research output: Contribution to journalArticle

Ágg, Bence ; Baranyai, Tamás ; Makkos, András ; Veto, Borbála ; Faragó, Nóra ; Zvara, A. ; Giricz, Z. ; Veres, Dániel V. ; Csermely, P. ; Arányi, T. ; Puskás, L. ; Varga, Zoltán V. ; Ferdinandy, Péter. / MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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