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 an NR_045363‐targeting lncRNA Smart silencer, and the apoptosis of CMs was analyzed by terminal‐deoxynucleoitidyl transferase mediated nick end labeling 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 tumor protein 53 (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 suggest 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 inhibition of the p53 pathway.

中文翻译：

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长的非编码RNA NR_045363涉及心肌细胞凋亡和通过p53信号途径的心脏修复。

长非编码RNA（lncRNA）可以参与各种生物学行为，包括调节细胞分化，增殖和凋亡。研究人员之前已经确认，高度保守的lncRNA NR_045363可控制心肌（CM）增殖和心脏修复。本研究调查了NR_045363对CM细胞凋亡的影响。对7天大的小鼠进行永久性左冠状动脉前降支结扎（LAD），并通过定量实时聚合酶链反应（qRT-PCR）分析了NR_045363的表达。术后第一周，MI组的NR_045363表达明显超过Sham组。使用靶向NR_045363的lncRNA Smart沉默子在原代培养的CM中敲低NR_045363的表达，然后通过末端脱氧核糖基转移酶介导的切口末端标记和Annexin-V / PI双重染色分析CMs的凋亡。这些目前的结果表明，NR_045363敲低显着促进了CMs的凋亡。为了研究潜在的机制，进行了RNA测序（RNA-seq），并使用了独创性途径分析（IPA）分析了RNA-seq结果。RNA-seq数据显示，在NR_045363组合型CM中，共有2,291个基因上调或下调，而IPA分析表明，肿瘤蛋白53（p53）是上游调节子。在体内，通过AAV9系统的NR_045363过表达改善了7日龄小鼠心肌梗死后的心脏功能，并抑制了CM凋亡。