LncRNA Kcnq1ot1 renders cardiomyocytes apoptosis in acute myocardial infarction model by up-regulating Tead1

• Published in: Life sciences (1973) Vol. 256; p. 117811
• Main Authors: Liao, Bihong, Dong, Shaohong, Xu, Zhenglei, Gao, Fei, Zhang, Suihao, Liang, Ruijuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2020; Elsevier BV
• Subjects: Acute myocardial infarction; Apoptosis; Assaying; Cardiomyocytes; Cardiovascular diseases; Coronary artery; Flow cytometry; Heart attacks; Hypoxia; Injuries; KCNQ1 protein; Kcnq1ot1; KCNQ1OT1 protein; miR-466i-5p; miR-466k; Myocardial infarction; Myocardium; Potassium channels (voltage-gated); Tead1; Kcnq1ot1; miR-466k; Tead1; Acute myocardial infarction; Urethane (CAS:51-79-6;_Sigma-Aldrich, St. Louis, Missouri, USA); miR-466i-5p
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117811

Acute myocardial infarction (AMI) is a major cardiovascular disease with high mortality worldwide. Hypoxia is a key inducing factor for AMI. We aimed to examine the expression and functions of Kcnq1ot1 (KCNQ1 overlapping transcript 1) in hypoxia-induced cardiomyocytes in the process of AMI. The left anterior descending coronary artery ligation (LAD) was used for inducing in-vivo AMI model and the primary cardiomyocytes were extracted; in-vitro H9c2 cell model was simulated by hypoxia treatment. TUNEL, flow cytometry and JC-1 assay were carried out to evaluate cell apoptosis. Mechanism assays including luciferase reporter assay and RIP assay revealed interplays between RNAs. To begin with, Kcnq1ot1 was revealed to be conspicuously upregulated in myocardium infracted zone and border zone within 2 days since establishment of the model. Moreover, inhibition of Kcnq1ot1 protected cardiomyocytes against hypoxia-triggered cell apoptosis during the process of AMI. Then, miR-466k and miR-466i-5p were proved to bind with Kcnq1ot1 and participated in Kcnq1ot1-mediated cardiomyocyte injury under hypoxia. Subsequently, Kcnq1ot1 was found to elevate Tead1 (TEA domain transcription factor 1) expression via sponging miR-466k and miR-466i-5p. Finally, it was verified that Kcnq1ot1 regulated hypoxia-induced cardiomyocyte injury dependent on Tead1. In conclusion, Kcnq1ot1 sponged miR-466k and miR-466i-5p to up-regulate Tead1, thus triggering cardiomyocyte injury in the process of AMI. [Display omitted]