Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes

• DOI: 10.1161/circresaha.112.277418
• Publication Date: 2012-08-14T02:43:06Z
• 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
• Keywords: Heart Failure; 0301 basic medicine; Computational Biology; Membrane Proteins; Aortic Valve Stenosis; Rats; Up-Regulation; MicroRNAs; Sarcoplasmic Reticulum; 03 medical and health sciences; Models, Animal; Animals; Calcium; Myocytes, Cardiac; RNA, Messenger; Cells, Cultured; Excitation Contraction Coupling

Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as major mechanism underlying defective E-C However, regulatory JP2 remains unknown.To determine whether microRNAs regulate expression.Bioinformatic analysis predicted 2 potential binding sites miR-24 in 3'-untranslated regions mRNA. Luciferase assays confirmed that suppressed expression by either these sites. In aortic stenosis model, was upregulated failing cardiomyocytes. Adenovirus-directed overexpression and reduced Ca(2+) transient amplitude coupling gain.MiR-24-mediated suppression provides novel molecular for regulation heart cells suggests new target against failure.