Critical role of SIRT1 upregulation on the protective effect of lncRNA ANRIL against hypoxia/reoxygenation injury in H9c2 cardiomyocytes

Song,Binghui; Wei,Dongmei; Yin,Gang; Song,Xiaoguang; Wang,Shuqing; Jia,Shanshan; Zhang,Jidong; Li,Longhu; Wu,Xiaofei

doi:10.3892/mmr.2021.12186

Critical role of SIRT1 upregulation on the protective effect of lncRNA ANRIL against hypoxia/reoxygenation injury in H9c2 cardiomyocytes

Authors:
- Binghui Song
- Dongmei Wei
- Gang Yin
- Xiaoguang Song
- Shuqing Wang
- Shanshan Jia
- Jidong Zhang
- Longhu Li
- Xiaofei Wu
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Affiliations: Internal Medicine‑Cardiovascular Department, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161005, P.R. China, Department of Traditional Chinese Geriatric Medicine, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161005, P.R. China, Department of Research Section, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161005, P.R. China, Department of GI Medicine, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161005, P.R. China, Department of Statistics Section, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161005, P.R. China
Published online on: June 2, 2021 https://doi.org/10.3892/mmr.2021.12186
Article Number: 547
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dysregulation of long non‑coding RNA (IncRNA) antisense non‑coding RNA in the INK4 locus (ANRIL) is associated with the risk of myocardial infarction (MI). Therefore, the present study aimed to determine the mechanisms underlying this association, which is currently poorly understood, to the best of our knowledge. The current study used an in vitro myocardial ischemia and reperfusion (MI/R) model, in which H9c2 cardiomyocytes were exposed to hypoxia/reoxygenation (H/R), which demonstrated that ANRIL expression was downregulated and that ANRIL positively regulated sirtuin 1 (SIRT1) expression following H/R injury. Subsequently, it was demonstrated that ANRIL upregulated SIRT1 expression by sponging microRNA‑181a (miR‑181a). In addition, ANRIL overexpression reduced lactate dehydrogenase release and apoptosis of H9c2 cardiomyocytes exposed to H/R, indicating that ANRIL prevented H/R‑induced cardiomyocyte injury. Moreover, both miR‑181a overexpression and SIRT1 knockdown significantly decreased the protective effects of ANRIL on H/R‑induced cardiomyocyte injury, thus demonstrating that SIRT1 upregulation via sponging miR‑181a is a critical mechanism that mediates the function of ANRIL. These results provided a novel mechanistic insight into the role of ANRIL in H/R‑injured cardiomyocytes and suggested that the ANRIL/miR‑181a/SIRT1 axis may be a therapeutic target for reducing MI/R injury.

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