Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Cell Signal. 2023 Dec;112:110919. doi: 10.1016/j.cellsig.2023.110919. Epub 2023 Oct 15.
Myocardial infarction(MI) causes prolonged ischemia of infarcted myocardial tissue, which triggers a wide range of hypoxia cellular responses in cardiomyocytes. Emerging evidence has indicated the critical roles of long non-coding RNAs(lncRNAs) in cardiovascular diseases, including MI. The purpose of this study was to investigate the roles of lncRNA H19 and H19/HIF-1α pathway during MI. Results showed that cell injury and mitochondrial dysfunction were induced in hypoxia-treated H9c2 cells, accompanied by an increase in the expression of H19. H19 silencing remarkably diminishes cell injury, inhibits the dysfunctional degree of mitochondria, and decreases the injury of MI rats. Bioinformatics analysis and dual-luciferase assays revealed that H19 was the hypoxia-responsive lncRNA, and HIF-1α induced H19 transcription through direct binding to the H19 promoter. Moreover, H19 participates in the HIF-1α pathway by stabilizing the HIF-1α protein. These results indicated that H19 might be a potential biomarker and therapeutic target for myocardial infarction.
心肌梗死（MI）导致梗死心肌组织长时间缺血，从而引发心肌细胞中广泛的缺氧细胞反应。新出现的证据表明，长链非编码 RNA（lncRNA）在心血管疾病中具有重要作用，包括 MI。本研究旨在探讨 lncRNA H19 和 H19/HIF-1α 通路在 MI 中的作用。结果表明，缺氧处理的 H9c2 细胞诱导细胞损伤和线粒体功能障碍，同时 H19 的表达增加。H19 沉默显著减少细胞损伤，抑制线粒体功能障碍程度，并减少 MI 大鼠的损伤。生物信息学分析和双荧光素酶报告基因检测表明，H19 是缺氧反应性 lncRNA，HIF-1α 通过直接结合 H19 启动子诱导 H19 转录。此外，H19 通过稳定 HIF-1α 蛋白参与 HIF-1α 通路。这些结果表明，H19 可能是心肌梗死的潜在生物标志物和治疗靶点。
