Our study was aimed at exploring the roles of lncRNA RP11-400K9.4 (RP11-400K9.4) on hypoxia/reoxygenation (H/R) -induced cardiomyocytes apoptosis. H/R model was constructed in rat primary cardiomyocytes (PC) and H9c2 cells. In this study, the results showed that H/R significantly induced the apoptosis of PC and H9c2 cells. The expression of RP11-400K9.4 was upregulated in H/R-induced PC and H9c2 cells, but miR-423 expression was downregulated. Silencing RP11-400K9.4 could attenuate H/R-induced apoptosis in PC and H9c2 cells. We also found that miR-423 was a potential target of RP11-400K9.4. The effect of silencing RP11-400K9.4 on H/R-induced apoptosis of PC and H9c2 cells was significantly reversed by miR-423 inhibitor transfection. Furthermore, our data confirmed that silencing RP11-400K9.4 promoted the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) /extracellular signal-regulated kinase (ERK) pathways and these phenomena can be reversed by miR-423 inhibitor transfection. In conclusion, our study demonstrated that silencing RP11-400K9.4 could alleviate H/R-induced cardiomyocytes damages via suppressing apoptosis by targeting miR-423 with the activation of PI3K/AKT and MEK/ERK signaling pathways.

我们的研究旨在探索 lncRNA RP11-400K9.4 (RP11-400K9.4) 在缺氧/复氧 (H/R) 诱导的心肌细胞凋亡中的作用。在大鼠原代心肌细胞 (PC) 和 H9c2 细胞中构建 H/R 模型。本研究结果显示H/R显着诱导PC和H9c2细胞凋亡。RP11-400K9.4在H/R诱导的PC和H9c2细胞中表达上调，而miR-423表达下调。沉默 RP11-400K9.4 可以减弱 H/R 诱导的 PC 和 H9c2 细胞凋亡。我们还发现 miR-423 是 RP11-400K9.4 的潜在靶标。miR-423抑制剂转染显着逆转了沉默RP11-400K9.4对H/R诱导的PC和H9c2细胞凋亡的影响。此外，我们的数据证实沉默 RP11-400K9。4促进磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）和丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK）/细胞外信号调节激酶（ERK）通路的激活，这些现象可以通过以下方式逆转miR-423抑制剂转染。总之，我们的研究表明，沉默 RP11-400K9.4 可以通过激活 PI3K/AKT 和 MEK/ERK 信号通路来靶向 miR-423，从而抑制细胞凋亡，从而减轻 H/R 诱导的心肌细胞损伤。