Back to Search
Start Over
Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarction.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2019 Dec; Vol. 23 (12), pp. 8369-8380. Date of Electronic Publication: 2019 Oct 20. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Animals
Animals, Newborn
Cell Hypoxia
Cells, Cultured
Disease Models, Animal
Gene Knockdown Techniques
Humans
Male
Mice, Inbred C57BL
Mice, Inbred ICR
Myocardial Infarction metabolism
Myocytes, Cardiac cytology
Myocytes, Cardiac metabolism
Tumor Suppressor Protein p53 metabolism
Apoptosis genetics
Endoplasmic Reticulum Stress genetics
Gene Expression Regulation
Myocardial Infarction genetics
RNA, Long Noncoding genetics
Tumor Suppressor Protein p53 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 23
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31631486
- Full Text :
- https://doi.org/10.1111/jcmm.14714