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...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Ágg Bence
Baranyai Tamás
Makkos András
Vető Borbála
Faragó Nóra
Zvara Ágnes
Giricz Zoltán
Veres Dániel
Csermely Péter
Arányi Tamás
Puskás László
Varga Zoltán
Ferdinandy Péter
Dokumentumtípus: Cikk
Megjelent: 2018
Sorozat:SCIENTIFIC REPORTS 8 No. 1
doi:10.1038/s41598-018-27740-3

mtmt:3399465
Online Access:http://publicatio.bibl.u-szeged.hu/20547
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245 1 0 |a MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium  |h [elektronikus dokumentum] /  |c  Ágg Bence 
260 |c 2018 
300 |a Terjedelem:11-Azonosító:10134 
490 0 |a SCIENTIFIC REPORTS  |v 8 No. 1 
520 3 |a 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. 
700 0 1 |a Baranyai Tamás  |e aut 
700 0 1 |a Makkos András  |e aut 
700 0 1 |a Vető Borbála  |e aut 
700 0 1 |a Faragó Nóra  |e aut 
700 0 1 |a Zvara Ágnes  |e aut 
700 0 1 |a Giricz Zoltán  |e aut 
700 0 1 |a Veres Dániel  |e aut 
700 0 1 |a Csermely Péter  |e aut 
700 0 1 |a Arányi Tamás  |e aut 
700 0 1 |a Puskás László  |e aut 
700 0 1 |a Varga Zoltán  |e aut 
700 0 1 |a Ferdinandy Péter  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/20547/1/s41598_018_27740_3_u.pdf  |z Dokumentum-elérés