| Title | Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes |
| Authors | Xu, Ming Wu, Hao-Di Li, Rong-Chang Zhang, Hai-Bo Wang, Meng Tao, Jin Feng, Xin-Heng Guo, Yun-Bo Li, Su-Fang Lai, Shao-Ting Zhou, Peng Li, Lin-Lin Yang, Hua-Qian Luo, Guan-Zheng Bai, Yan Xi, Jianzhong J. Gao, Wei Han, Qi-De Zhang, You-Yi Wang, Xiu-Jie Meng, Xu Wang, Shi-Qiang |
| Affiliation | Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Hosp 3,Coll Engn, Beijing 100871, Peoples R China. Capital Med Univ, Anzhen Hosp, Beijing, Peoples R China. Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China. |
| Keywords | myocardial contractility excitation-contraction coupling heart failure calcium signaling heart failure HEART-FAILURE CARDIAC-HYPERTROPHY CHANNEL FAMILY CELLS |
| Issue Date | 2012 |
| Publisher | circulation research |
| Citation | CIRCULATION RESEARCH.2012,111,(7),837-841. |
| 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 Ca2+ 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. (Circ Res. 2012;111:837-841.) |
| URI | http://hdl.handle.net/20.500.11897/315942 |
| ISSN | 0009-7330 |
| DOI | 10.1161/CIRCRESAHA.112.277418 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 第三医院 |
