Long non‐coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress‐mediated apoptosis by targeting p53 following myocardial infarction

• Published in: Journal of cellular and molecular medicine Vol. 23; no. 12; pp. 8369 - 8380
• Main Authors: Li, Xueling, Zhao, Jinxuan, Geng, Jin, Chen, Fu, Wei, Zilun, Liu, Chen, Zhang, Xinlin, Li, Qiaoling, Zhang, Jingmei, Gao, Ling, Xie, Jun, Xu, Biao
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2019; John Wiley and Sons Inc
• Subjects: Animals; Animals, Newborn; Apoptosis; Apoptosis - genetics; Cardiac muscle; cardiomyocyte apoptosis; Cardiomyocytes; Caspase-12; Cell culture; Cell Hypoxia; Cells, Cultured; Disease Models, Animal; Endoplasmic reticulum; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - genetics; Experiments; Gene Expression Regulation; Gene Knockdown Techniques; Heart; Heart attacks; Humans; Hypoxia; Laboratory animals; lncRNA MEG3; Male; Medical research; Mice, Inbred C57BL; Mice, Inbred ICR; MicroRNAs; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Neonates; Original; Ostomy; p53; p53 Protein; Reactive oxygen species; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Science; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Variance analysis; Ventricle; lncRNA MEG3; cardiomyocyte apoptosis; endoplasmic reticulum stress; myocardial infarction; p53
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14714

Mounting evidence has indicated that long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) regulates cell apoptosis, and is involved in a variety of diseases. However, its exact role in myocardial infarction (MI) has not been fully elucidated. In the present study, we firstly observed that the expression levels of the lncRNA MEG3 in infarct hearts and hypoxic neonatal mice ventricular myocytes (NMVMs) were up‐regulated by quantitative real‐time PCR (qRT‐PCR). Then, we knocked down lncRNA MEG3 by lentiviral delivery in the myocardial border region following multipoint injection. Following 28 days of MI, the lncRNA MEG3 knockdown mice indicated better cardiac function, and less cardiac remodelling by ultrasonic cardiogram and histological analysis. In addition, we indicated that lncRNA MEG3 knockdown reduced myocyte apoptosis and reactive oxygen species production in MI mice model and hypoxic NMVMs. Furthermore, we revealed that knockdown of lncRNA MEG3 protected against endoplasmic reticulum stress (ERS)‐mediated myocardial apoptosis including the induction of PERK‐eIF2α and caspase 12 pathways. At last, we provided evidence that p53 was identified as a protein target of lncRNA MEG3 to regulate NF‐κB‐ and ERS‐associated apoptosis. Taken collectively, our findings demonstrated that lncRNA MEG3 knockdown exerted cardioprotection by reducing ERS‐mediated apoptosis through targeting p53 post‐MI.