LAUSR

Long noncoding RNAs (lncRNAs) can participate in various biological behaviors, including regulating cell differentiation, proliferation and apoptosis. The investigators have previously confirmed that highly conserved lncRNA NR_045363 controls cardiomyocyte (CM) proliferation and cardiac repair. The present study investigates the effects of NR_045363 on CM apoptosis. Seven-day-old mice were subjected to permanent left anterior descending coronary artery ligation (LAD), and the NR_045363 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of NR_045363 in the MI group significantly exceeded the Sham group during the first week after the operation. The NR_045363 expression was knocked down in primary cultured CMs using a NR_045363-targeting LncRNA Smart silencer, and the apoptosis of CMs was analyzed by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) and Annexin-V/PI double staining. These present results indicate that the NR_045363 knockdown significantly promoted the apoptosis of CMs. In order to investigate the underlying mechanism, RNA-sequencing (RNA-seq) was performed, and ingenuity pathway analysis (IPA) was used to analyze the RNA-seq results. The RNA-seq data revealed that a total of 2,291 genes were upregulated or downregulated in NR_045363 knockdown CMs, and the IPA analysis indicated that p53 was the upstream regulator. In vivo, the NR_045363 overexpression through the AAV9 system improved the heart function after MI in 7-day-old mice and inhibited the CM apoptosis. These data suggests that NR_045363 is involved in CM apoptosis, and that NR_045363 overexpression exerts positive effects on cardiac repair by alleviating CM apoptosis through the activation of the p53 pathway. This article is protected by copyright. All rights reserved.