Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, China.
J Cardiovasc Pharmacol. 2020 Jul;76(1):77-85. doi: 10.1097/FJC.0000000000000845.
Increasing evidence has confirmed that both long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) exert key roles in the pathogenesis of myocardial infarction (MI). Previous microarray assay results revealed that lncRNA LNC_000898 expression was significantly downregulated in acute MI. However, the specific function of LNC_000898 on MI is still unclear. Our study was aimed to explore the role of LNC_000898 on cardiac MI injury and investigate its underlying mechanism. The male C57BL/6 mouse was used as cardiac MI injury animal models, and neonatal mouse ventricular cardiomyocytes (NMCMs) exposed to hypoxia were used as an in vitro model. Quantitative real-time polymerase chain reaction analysis, Western blot analysis, Tunel immunofluorescence staining assay, and cardiac echocardiography measurement were conducted to detect corresponding indicators. The results indicated that LNC_000898 expression was downregulated in marginal tissue of MI and in NMCMs exposed to hypoxia. Overexpression of LNC_000898 decreased cardiomyocyte apoptosis both in vivo and in vitro. In addition, we elaborated that LNC_000898 exerts its inhibitory effect on apoptosis after MI through the miR-375/PDK1 axis. Through miR-375 overexpression or silencing PDK1, the biological effects of LNC_000898 on hypoxia-induced NMCM injury were partially reversed. These data not only demonstrate that LNC_000898 could protect the heart against MI injury by regulating miR-375/PDK1 but also provide a new understanding to better protection of MI injury through the LNC_000898/miR-375/PDK1 axis.
越来越多的证据证实，长链非编码 RNA（lncRNA）和 microRNA（miRNA）在心肌梗死（MI）的发病机制中发挥关键作用。先前的微阵列分析结果表明，lncRNA LNC_000898 在急性 MI 中的表达显著下调。然而，LNC_000898 对 MI 的具体功能仍不清楚。本研究旨在探讨 LNC_000898 对心肌 MI 损伤的作用，并研究其潜在机制。雄性 C57BL/6 小鼠被用作心肌 MI 损伤动物模型，缺氧暴露的新生小鼠心室心肌细胞（NMCMs）被用作体外模型。进行定量实时聚合酶链反应分析、Western blot 分析、Tunel 免疫荧光染色分析和心脏超声心动图测量，以检测相应的指标。结果表明，LNC_000898 的表达在 MI 的边缘组织和缺氧暴露的 NMCMs 中下调。LNC_000898 的过表达减少了体内和体外心肌细胞的凋亡。此外，我们阐述了 LNC_000898 通过 miR-375/PDK1 轴对 MI 后凋亡发挥抑制作用。通过 miR-375 的过表达或沉默 PDK1，LNC_000898 对缺氧诱导的 NMCM 损伤的生物学效应部分逆转。这些数据不仅表明 LNC_000898 可以通过调节 miR-375/PDK1 来保护心脏免受 MI 损伤，而且还为通过 LNC_000898/miR-375/PDK1 轴更好地保护 MI 损伤提供了新的认识。
