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

Yue,Qingxiong; Zhao,Cuiting; Wang,Yonghuai; Zhao,Lanting; Zhu,Qing; Li,Guangyuan; Wu,Nan; Jia,Dalin; Ma,Chunyan

doi:10.3892/mmr.2018.9593

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

Authors:
- Qingxiong Yue
- Cuiting Zhao
- Yonghuai Wang
- Lanting Zhao
- Qing Zhu
- Guangyuan Li
- Nan Wu
- Dalin Jia
- Chunyan Ma
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Affiliations: Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, The Core Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: October 25, 2018 https://doi.org/10.3892/mmr.2018.9593
Pages: 5742-5750

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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.

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