Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes

Overview

Journal Circ Res

Specialty Cardiology & Vascular Diseases

Date 2012 Aug 15

PMID 22891046

Citations 59

Authors

Ming Xu

Hao-Di Wu

Rong-Chang Li

Hai-Bo Zhang

Meng Wang

Jin Tao

Xin-Heng Feng

Yun-Bo Guo

Su-Fang Li

Shao-Ting Lai

Peng Zhou

Lin-Lin Li

Hua-Qian Yang

Guan-Zheng Luo

Yan Bai

Jianzhong J Xi

Wei Gao

Qi-De Han

You-Yi Zhang

Xiu-Jie Wang

Xu Meng

Shi-Qiang Wang

Affiliations

Soon will be listed here.

Abstract

Rationale: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown.

Objective: To determine whether microRNAs regulate JP2 expression.

Methods And Results: Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3'-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca(2+) transient amplitude and E-C coupling gain.

Conclusions: MiR-24-mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure.

Citing Articles

Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.

Wang J, Chen B, Shi Q, Ciampa G, Zhao W, Zhang G Circulation. 2024; 151(2):171-187.

PMID: 39291390 PMC: 11729472. DOI: 10.1161/CIRCULATIONAHA.124.069329.

Structure, Function, and Regulation of the Junctophilin Family.

Hall D, Takeshima H, Song L Annu Rev Physiol. 2023; 86:123-147.

PMID: 37931168 PMC: 10922073. DOI: 10.1146/annurev-physiol-042022-014926.

Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation.

Zhong Z, Li X, Gao L, Wu X, Ye Y, Zhang X Cardiovasc Drugs Ther. 2023; .

PMID: 37702834 DOI: 10.1007/s10557-023-07491-8.

Augmenting workload drives T-tubule assembly in developing cardiomyocytes.

Manfra O, Louey S, Jonker S, Perdreau-Dahl H, Frisk M, Giraud G J Physiol. 2023; 602(18):4461-4486.

PMID: 37128962 PMC: 10854476. DOI: 10.1113/JP284538.

Suppression of RBFox2 by Multiple MiRNAs in Pressure Overload-Induced Heart Failure.

Gu M, Zhao Y, Wang H, Cheng W, Liu J, Ouyang K Int J Mol Sci. 2023; 24(2).

PMID: 36674797 PMC: 9867119. DOI: 10.3390/ijms24021283.

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