Cardiac hypertrophy has been a high prevalence rate throughout the world. It has posed a big threat to public health due to limited therapeutic approaches. Previous studies showed that pathological cardiac hypertrophy was associated with autophagy, microRNAs (miRNA), and other signaling pathways, while the molecular mechanisms remain incompletely characterized. In this study, we used thoracic aortic constriction (TAC)-induced mice and angiotensin-II (Ang-II)-induced H9C2 cell line as cardiac hypertrophy model to investigate the role of miR-26a-5p in cardiac hypertrophy. We found that miR-26a-5p was downregulated in cardiac hypertrophy mice. Overexpression of miR-26a-5p by type 9 recombinant adeno-associated virus (rAAV9) reversed the heart hypertrophic manifestations. The phenotypes were also promoted by miR-26a-5p inhibitor in Ang-II-induced H9C2 cells. Through miRNA profile analysis and dual-luciferase reporter assay, ADAM17 was identified as a direct target of miR-26a-5p. Restored expression of ADAM17 disrupted the effect of miR-26a-5p on cardiac hypertrophy. To sum up, these results indicated that miR-26a-5p played an inhibitory role in cardiac hypertrophy and dysfunction via targeting ADAM17. The miR-26a-5p-ADAM17-cardiac hypertrophy axis provided special insight and a new molecular mechanism for a better understanding of cardiac hypertrophy disease, as well as the diagnostic and therapeutic practice.

中文翻译：

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MiR-26a-5p 通过靶向 ADAM17 缓解心脏肥大和功能障碍

心脏肥大在世界范围内一直是高患病率。由于治疗方法有限，它对公众健康构成了巨大威胁。先前的研究表明，病理性心脏肥大与自噬、microRNAs (miRNA) 和其他信号通路有关，而分子机制仍未完全表征。在本研究中，我们使用胸主动脉缩窄 (TAC) 诱导的小鼠和血管紧张素-II (Ang-II) 诱导的 H9C2 细胞系作为心肌肥大模型，研究 miR-26a-5p 在心肌肥大中的作用。我们发现 miR-26a-5p 在心脏肥大小鼠中下调。9 型重组腺相关病毒 (rAAV9) 过表达 miR-26a-5p 可逆转心脏肥大表现。在 Ang-II 诱导的 H9C2 细胞中，miR-26a-5p 抑制剂也促进了表型。通过 miRNA 谱分析和双荧光素酶报告基因分析，ADAM17 被鉴定为 miR-26a-5p 的直接靶标。ADAM17 的恢复表达破坏了 miR-26a-5p 对心脏肥大的影响。综上所述，这些结果表明 miR-26a-5p 通过靶向 ADAM17 在心脏肥大和功能障碍中发挥抑制作用。miR-26a-5p-ADAM17-心脏肥大轴为更好地了解心脏肥大疾病以及诊断和治疗实践提供了特殊的见解和新的分子机制。ADAM17 的恢复表达破坏了 miR-26a-5p 对心脏肥大的影响。综上所述，这些结果表明 miR-26a-5p 通过靶向 ADAM17 在心脏肥大和功能障碍中发挥抑制作用。miR-26a-5p-ADAM17-心脏肥大轴为更好地了解心脏肥大疾病以及诊断和治疗实践提供了特殊的见解和新的分子机制。ADAM17 的恢复表达破坏了 miR-26a-5p 对心脏肥大的影响。综上所述，这些结果表明 miR-26a-5p 通过靶向 ADAM17 在心脏肥大和功能障碍中发挥抑制作用。miR-26a-5p-ADAM17-心脏肥大轴为更好地了解心脏肥大疾病以及诊断和治疗实践提供了特殊的见解和新的分子机制。