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

被引：24

作者：

Agg, Bence ^{[1
,2
,3
]}

Baranyai, Tamas ^{[1
]}

Makkos, Andras ^{[1
]}

Veto, Borbala ^{[4
]}

Farago, Nora ^{[5
]}

Zvara, Agnes ^{[5
]}

Giricz, Zoltan ^{[1
]}

Veres, Daniel V. ^{[6
]}

Csermely, Peter ^{[6
]}

Aranyi, Tamas ^{[4
]}

Puskas, Laszlo G. ^{[5
]}

Varga, Zoltan V. ^{[1
]}

Ferdinandy, Peter ^{[1
,2
,7
]}

机构：

[1] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary

[2] Pharmahungary Grp, H-6722 Szeged, Hungary

[3] Semmelweis Univ, Heart & Vasc Ctr, H-1122 Budapest, Hungary

[4] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1117 Budapest, Hungary

[5] Hungarian Acad Sci, Biol Res Ctr, Inst Genet, H-6726 Szeged, Hungary

[6] Semmelweis Univ, Dept Med Chem, H-1094 Budapest, Hungary

[7] Univ Szeged, Dept Biochem, Cardiovasc Res Grp, H-6720 Szeged, Hungary

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

BETA(2)-ADRENERGIC RECEPTOR; CARDIAC DYSFUNCTION; DIET LEADS; CHOLESTEROL; TARGET; RNA; LIPOPROTEINS; CALCINEURIN; INVOLVEMENT; RESOURCE;

D O I：

10.1038/s41598-018-27740-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：11

共 55 条

[1]

Diversifying microRNA sequence and function [J].