Long Noncoding RNA LNC_000898 Alleviates Cardiomyocyte Apoptosis and Promotes Cardiac Repair After Myocardial Infarction Through Modulating the miR-375/PDK1 Axis.

Abstract

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.