Positive feedback loop of lncRNA SNHG1/miR‑16‑5p/GATA4 in the regulation of hypoxia/reoxygenation‑induced cardiomyocyte injury

Gong,Juan; Dou,Luqun; Zhou,Yang

doi:10.3892/mmr.2021.12544

Positive feedback loop of lncRNA SNHG1/miR‑16‑5p/GATA4 in the regulation of hypoxia/reoxygenation‑induced cardiomyocyte injury

Authors:
- Juan Gong
- Luqun Dou
- Yang Zhou
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Affiliations: Department of Cardiothoracic Surgery, Leshan People's Hospital, Leshan, Sichuan 614000, P.R. China, Department of Cardiothoracic Surgery, Leshan People's Hospital, Leshan, Sichuan 614000, P.R. China
Published online on: November 25, 2021 https://doi.org/10.3892/mmr.2021.12544
Article Number: 28
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous studies have demonstrated that long non‑coding RNAs (lncRNAs) serve an important regulatory role in ischemic injury of cardiomyocytes. lncRNA small nucleolar RNA host gene 1 (SNHG1) could effectively protect cardiomyocytes against various injuries. However, the role of SNHG1 in ischemic cardiomyocyte injury is unclear. It was hypothesized that SNHG1 may have a protective effect on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) by sponging microRNA (miRNA/miR). The purpose of the present study was to explore the role and molecular mechanism of SNHG1 in ischemic cardiomyocyte injury. A H9c2 cardiomyocyte H/R model was established. The expression levels of SNHG1 in cardiomyocytes treated with H/R were detected using reverse transcription‑quantitative PCR. A luciferase reporter assay was used to analyze the associations among SNHG1, miR‑16‑5p and GATA binding protein 4 (GATA4). Chromatin immunoprecipitation experiments were performed to analyze the interaction between SNHG1 and GATA4. Cell Counting Kit‑8, enzyme‑linked immunosorbent assay, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling and western blotting experiments were used to detect cell activity, lactate dehydrogenase release, apoptosis and apoptosis‑related proteins (Bcl‑2, Bax, Cleaved caspase‑3 and Cleaved caspase‑9), respectively. The expression levels of SNHG1 were downregulated in cardiomyocytes treated with H/R. Overexpression of SNHG1 had a protective effect on cardiomyocyte injury induced by H/R. In addition, SNHG1 could regulate the expression levels of GATA4 via sponging of miR‑16‑5p. Further experiments revealed that GATA4 could bind to the promoter region of SNHG1 and subsequently regulated the expression levels of SNHG1, indicating the important role of the positive feedback loop of SNHG1/miR‑16‑5p/GATA4 in cardiomyocyte ischemic injury. To conclude, the present study revealed the protective effect of the SNHG1/miR‑16‑5p/GATA4 positive feedback loop on cardiomyocyte injury induced by H/R and provided a potential therapeutic target for ischemic cardiomyocyte injury.

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