Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 12, Pages 8369-8380Publisher
WILEY
DOI: 10.1111/jcmm.14714
Keywords
cardiomyocyte apoptosis; endoplasmic reticulum stress; lncRNA MEG3; myocardial infarction; p53
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Funding
- National Science Foundations of China [81470371]
- Programs of the Science Foundation in Nanjing [201605015, YKK15061, ZKX17011]
- Natural Science Foundation of Jiangsu Province [BK20150106]
- Key Projects of Science and Techology of Jiangsu Province [BE2016607]
- Funds for Jiangsu Provincial Key Medical Discipline [ZDXKB2016013]
- Medical and Health Science and Technology Project of Zhejiang Province [2019RC018, 2019330974]
- Nanjing Medical Science and Technique Development Foundation [QRX17113]
- Funds for Jiangsu Provincial Medical Youth Talent [Q201610, QNRC2016033]
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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-eIF2 alpha and caspase 12 pathways. At last, we provided evidence that p53 was identified as a protein target of lncRNA MEG3 to regulate NF-kappa B- 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.
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