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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53
Xueling Li1,2, Jinxuan Zhao2, Jin Geng3
1Department of Cardiology, Zhejiang provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
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.
Insights
Long non-coding RNA MEG3 knockdown improves heart function after myocardial infarction by reducing cell death and endoplasmic reticulum stress. This study reveals lncRNA MEG3 as a therapeutic target for heart attack recovery.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- RNA Biology
Background:
- Long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) is implicated in various diseases.
- The specific role of lncRNA MEG3 in myocardial infarction (MI) remains unclear.
Purpose of the Study:
- To investigate the role of lncRNA MEG3 in myocardial infarction.
- To explore the therapeutic potential of targeting lncRNA MEG3 in post-MI recovery.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure lncRNA MEG3 expression.
- Lentiviral delivery to knockdown lncRNA MEG3 in a mouse MI model.
- Ultrasonic cardiogram and histological analysis for cardiac function and remodeling assessment.
- Assessment of myocyte apoptosis, reactive oxygen species, and endoplasmic reticulum stress (ERS) pathways.
Main Results:
- lncRNA MEG3 expression was upregulated in infarct hearts and hypoxic cardiomyocytes.
- Knockdown of lncRNA MEG3 improved cardiac function and reduced cardiac remodeling post-MI.
- lncRNA MEG3 knockdown decreased myocyte apoptosis, reactive oxygen species, and ERS.
- p53 was identified as a target of lncRNA MEG3, regulating NF-κB and ERS-associated apoptosis.
Conclusions:
- lncRNA MEG3 knockdown exerts cardioprotection after myocardial infarction.
- This protective effect is mediated by reducing endoplasmic reticulum stress-induced apoptosis via targeting p53.
