Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR‐374a‐5p against myocardial I/R injury. In this study, we explored the role of lncRNA TTTY15 and its potential interaction mechanisms with miR‐374a‐5p in myocardial I/R injury. The expression of TTTY15 was increased both in vitro and in vivo after myocardial I/R injury models according to quantitative real‐time polymerase chain reaction. Various assays were conducted to evaluate the regulatory relationship among TTTY15, miR‐374a‐5p, FOXO1, and autophagy in H9c2 and HL‐1 cells. The results showed that TTTY15 suppresses autophagy and myocardial I/R injury by targeting miR‐374a‐5p. We found that TTTY15 regulates miR‐374a‐5p, thus affecting FOXO1 expression and autophagy in myocytes during I/R. Furthermore, in an in vivo mouse model of myocardial I/R injury, suppression of TTTY15 successfully alleviated myocardial I/R injury. Our results reveal a novel feedback mechanism in which TTTY15 regulates miRNA processing and a potential target in myocardial I/R injury. TTTY15 is a promising therapeutic target for treating myocardial I/R injury.

中文翻译：

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敲低 lncRNA TTTY15 通过 miR-374a-5p/ FOXO1 轴减轻心肌缺血再灌注损伤

心肌缺血/再灌注（I/R）损伤极大地促进了冠心病患者的心肌组织损伤，最终导致心力衰竭。长链非编码 RNA (lncRNA) 在心肌 I/R 损伤过程中具有新的作用。我们之前的工作揭示了 miR-374a-5p 对心肌 I/R 损伤的保护作用。在本研究中，我们探讨了 lncRNA TTTY15 的作用及其与 miR-374a-5p 在心肌 I/R 损伤中的潜在相互作用机制。根据定量实时聚合酶链反应，在心肌 I/R 损伤模型后，TTTY15 在体外和体内的表达均增加。进行了各种测定以评估 TTTY15、miR-374a-5p、FOXO1 和 H9c2 和 HL-1 细胞中的自噬之间的调节关系。结果表明，TTTY15 通过靶向 miR-374a-5p 抑制自噬和心肌 I/R 损伤。我们发现 TTTY15 调节 miR-374a-5p，从而影响 I/R 期间肌细胞中 FOXO1 的表达和自噬。此外，在心肌 I/R 损伤的体内小鼠模型中，TTTY15 的抑制成功地减轻了心肌 I/R 损伤。我们的研究结果揭示了一种新的反馈机制，其中 TTTY15 调节 miRNA 加工和心肌 I/R 损伤的潜在靶点。TTTY15 是治疗心肌 I/R 损伤的有希望的治疗靶点。我们的研究结果揭示了一种新的反馈机制，其中 TTTY15 调节 miRNA 加工和心肌 I/R 损伤的潜在靶点。TTTY15 是治疗心肌 I/R 损伤的有希望的治疗靶点。我们的研究结果揭示了一种新的反馈机制，其中 TTTY15 调节 miRNA 加工和心肌 I/R 损伤的潜在靶点。TTTY15 是治疗心肌 I/R 损伤的有希望的治疗靶点。