LncRNA XR_595552 inhibition alleviates intermittent hypoxia-induced cardiomyocyte damage via activating the PI3K/AKT pathway.

Abstract

Although the long noncoding RNAs (lncRNAs) expression profiles have been observed in previous study, the biological functions and underlying mechanisms of lncRNAs in OSA-related cardiac injury have not been elucidated. In the present study, we investigated a novel lncRNA, lncRNA XR_595552, and evaluated its role in intermittent hypoxia (IH)-induced damage in H9c2 cardiomyocytes. H9c2 cells were exposed to IH condition. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression changes of lncRNA XR_595552 in H9c2 cells stimulated by IH. H9c2 cells were subjected to IH after transfection. CCK-8 was used to evaluate cell viability, and apoptosis was analyzed by Western blotting. Additionally, the regulatory relationship between lncRNA XR_595552 and PI3K/AKT was tested by RT-qPCR and Western blot. IH significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis). lncRNA XR_595552 was upregulated in a cell model of IH. Inhibition of lncRNA XR_595552 protected H9c2 cells against IH-induced damage, as the viability was increased, Bax, Caspase-9, and Caspase-3 were downregulated, and Bcl-2 was upregulated. More interestingly, lncRNA XR_595552 downregulation activated thePI3K/AKT pathway. Blockingthe PI3K/AKT signal pathway by the use of LY294002 eliminated the myocardioprotective effects of lncRNA XR_595552 in H9c2 cells under IH condition. The results show that lncRNA XR_595552, a novel lncRNA, may play a protective role in attenuating IH-induced injury in cardiomyocytes via aregulating PI3K/AKT pathway. The findings suggest that this lncRNA could serve as a therapeutic target to treat OSA-related cardiovascular disorders.