Long non‐coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress‐mediated apoptosis by targeting p53 following myocardial infarction
| Autor: | Jin Geng, Jingmei Zhang, Jinxuan Zhao, Biao Xu, Fu Chen, Jun Xie, Xueling Li, Xinlin Zhang, Zilun Wei, Ling Gao, Chen Liu, Qiaoling Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
p53 0301 basic medicine Myocardial Infarction Apoptosis Biology 03 medical and health sciences 0302 clinical medicine Gene expression Animals Humans lncRNA MEG3 Myocytes Cardiac Cells Cultured chemistry.chemical_classification Cardioprotection MEG3 Mice Inbred ICR Reactive oxygen species Gene knockdown Endoplasmic reticulum cardiomyocyte apoptosis Original Articles Cell Biology Endoplasmic Reticulum Stress Cell Hypoxia Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Animals Newborn Gene Expression Regulation chemistry Gene Knockdown Techniques 030220 oncology & carcinogenesis biology.protein Molecular Medicine RNA Long Noncoding Original Article Tumor Suppressor Protein p53 Caspase 12 |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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