Long non‐coding RNA DANCR alleviates acute myocardial infarction damage via regulating microRNA‐509‐5p/KLF transcription factor 13 pathway

• Published in: The Kaohsiung journal of medical sciences 2023-07, Vol.39 (7), p.652-664
• Main Authors: Tian, Yun‐Tao, Sun, Hua‐Xin, Zhou, Xian‐Hui, Tang, Bao‐Peng
• Format: Article
• Language: English
• Subjects: acute myocardial infarction; Adenosine triphosphate; Apoptosis; Apoptosis - genetics; Biomarkers; Biotechnology; Cardiomyocytes; Cardiovascular diseases; Cell Proliferation - genetics; Cytokines; Development and progression; Enzymes; Health aspects; Heart; Heart attack; Heart attacks; Heart failure; Humans; Hypoxia; Injuries; Ischemia; Kinases; KLF13; lncRNA DANCR; Luciferase; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐509‐5p; Muscle proteins; Myocardial Infarction - genetics; Proteins; Pulmonary arteries; Reactive oxygen species; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Transcription Factors; Tumor necrosis factor-TNF
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1002/kjm2.12680

Acute myocardial infarction (AMI) is the most important cause of death among cardiovascular diseases. Long noncoding RNAs (lncRNAs) have been widely implicated in the regulation of AMI progression. Discrimination antagonizing nonprotein coding RNA (DANCR) alleviated hypoxia‐caused cardiomyocyte damages, and the underlying mechanisms remain unclear. Here, we investigated the function and mechanism of DANCR in hypoxia‐induced cardiomyocytes and AMI model by enzyme‐linked immunosorbent assay, reactive oxygen species and adenosine triphosphate measurement, and mitochondrial activity determination. Additionally, luciferase reporter assay, immunoblotting, and qRT‐PCR were performed to validate the interactions between DANCR/miR‐509‐5p and miR‐509‐5p/Kruppel‐like factor 13 (KLF13). The role of DANCR was also verified in AMI model by overexpression. Our results showed that DANCR expression was significantly downregulated in hypoxia‐induced cardiomyocytes or AMI model. Overexpression of DANCR significantly alleviated mitochondrial damages, reduced inflammation, and improved cardiac function in the AMI model. Furthermore, we demonstrated that miR‐509‐5p/KLF13 axis mediated the protective effect of DANCR. The current study highlighted the critical role of DANCR in alleviating AMI progression through targeting the miR‐509‐5p/KLF13 signaling axis, suggesting that DANCR may serve as a potential diagnostic marker or therapeutic target for AMI.