MicroRNA and mitofusin-2 (Mfn2) are important in the development of cardiac hypertrophy, but the target relationship and mechanism associated with Ca²⁺ handling between SR and mitochondria under hypertrophic condition is not established. Mfn2 expression, Mfn2-mediated interorganelle Ca²⁺ cross-talk, and target regulation by miRNA-20b (miR-20b) were evaluated using animal/cellular hypertrophic models with state-of-art techniques. The results demonstrated that Mfn2 was down-regulated and miR-20b was up-regulated upon the target binding profile under hypertrophic condition. Our data showed that miR-20b induced cardiac hypertrophy that was reversed by rAAV9-anti-miR-20b or AMO-20b. The deleterious action of miR-20b on Mfn2 expression/function and mitochondrial ATP synthesis was observed and reversed by rAAV9-anti-miR-20b or AMO-20b. The targeted regulation of miR-20b on Mfn2 was confirmed by luciferase reporter and microRNA-masking. Importantly, the facts that mitochondrial calcium uniporter (MCU) activation by Spermine increased the cytosolic Ca²⁺ into mitochondria, manifested as enhanced histamine-mediated Ca²⁺ release from mitochondrial, suggesting that Ca²⁺ reuptake/buffering capability of mitochondria to cytosolic Ca²⁺ is injured by miR-20b-mediated Mfn2 signaling, by which leads cytosolic Ca²⁺ overload and cardiac hypertrophy through Ca²⁺ signaling pathway. In conclusion, pro-hypertonic miR-20b plays crucial roles in cardiac hypertrophy through down-regulation of Mfn2 and cytosolic Ca²⁺ overload by weakening the buffering capability of mitochondria.

MicroRNA和mitofusin-2（Mfn2）在心肌肥大的发展中很重要，但在肥厚条件下，SR和线粒体之间Ca ²⁺处理的靶标关系和机制尚未建立。Mfn2表达，Mfn2介导的细胞间Ca ²⁺使用动物/细胞肥大性模型和最新技术评估了miRNA-20b（miR-20b）的串扰和靶标调控。结果表明，在肥大条件下，Mfn2在靶结合谱上被下调，而miR-20b被上调。我们的数据表明，miR-20b诱导的心脏肥大被rAAV9-anti-miR-20b或AMO-20b逆转。观察到miR-20b对Mfn2表达/功能和线粒体ATP合成的有害作用，并被rAAV9-anti-miR-20b或AMO-20b逆转。萤光素酶报道分子和microRNA掩蔽证实了miR-20b对Mfn2的靶向调控。重要的是，精胺激活线粒体钙单向转运蛋白（MCU）的事实增加了胞质Ca ²⁺进入线粒体，表现为增强的组胺介导的线粒体Ca ²⁺释放，这表明miR-20b介导的Mfn2信号传导会损害线粒体Ca ²⁺对线粒体Ca ^2+的重摄取/缓冲能力，从而导致线粒体Ca ²⁺ Ca ²⁺信号通路引起超负荷和心肌肥大。总之，高渗前体miR-20b通过下调Mfn2和胞质Ca ²⁺超负荷，通过减弱线粒体的缓冲能力，在心脏肥大中起关键作用。