Downregulation of growth arrest-specific transcript 5 alleviates palmitic acid-induced myocardial inflammatory injury through the miR-26a/HMGB1/NF-κB axis

Abstract

Palmitic acid (PA) can induce lipotoxic damage to cardiomyocytes, although its precise mechanism of action has not been completely elucidated. Growth arrest-specific transcript 5 (GAS5) is a long noncoding RNA that serves a regulatory role in several pathological processes, including tumorigenesis, stroke, cardiac fibrosis and osteoarthritis; however, its role in PA-induced myocardial injury remains elusive. The present study aimed to explore the role and underlying mechanism of GAS5 on PA-induced myocardial injury. The expression of GAS5 in PA-treated cardiomyocytes (H9c2 cells) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its effects on PA-induced myocardial injury were measured by Cell Counting Kit-8 and lactate dehydrogenase (LDH) assays. The activities of cytokines and nuclear factor (NF)-κB were also detected by enzyme-linked immunosorbent assay, while interactions between GAS5 and microRNA (miR)-26a were evaluated by luciferase reporter assay and RT-qPCR. The regulation of GAS5 on high mobility group box 1 (HMGB1) expression was detected by RT-qPCR and western blotting. The results demonstrated that GAS5 was significantly upregulated in cardiomyocytes following treatment with PA. GAS5-knockdown increased the viability of PA-treated cardiomyocytes and reduced the activity of LDH, tumor necrosis factor-α and interleukin-1β. Furthermore, the present study identified that GAS5 specifically binds to miR-26a, and a reciprocal negative regulation exists between the two. The present study also demonstrated that GAS5 downregulation inhibited HMGB1 expression and NF-κB activation, while these suppressive effects were mediated by miR-26a. In conclusion, the present study demonstrated that PA can induce GAS5 expression and that the downregulation of GAS5 alleviated PA-induced myocardial inflammatory injury through the miR-26a/HMGB1/NF-κB axis. These data may provide a novel insight into the mechanism of myocardial lipotoxic injury.