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

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.

CircMEG3 inhibits telomerase activity by reducing Cbf5 in human liver cancer stem cells

“…45 Also, MEG3 inhibits the progression of prostate cancer by facilitating H3K27 trimethylation, 46 and MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis. 47 Furthermore, uric acid enhances autophagy through the MEG3/miR-7-5p/EGFR axis. 48 Interestingly, MEG3 interacts with miR-494 to repress bladder cancer progression through targeting PTEN, 49 and MEG3 binds with miR-27a to promote PHLPP2 protein translation and impairs bladder cancer invasion.…”

Role of long non‐coding RNAs in adipogenesis: State of the art and implications in obesity and obesity‐associated diseases

“…LncRNAs can also target the apoptotic process in cardiomyocytes, which can lead to myocardial infarction. P53 is also implicated in apoptosis modulation, and the lncRNA Meg3 can target p53 and subsequently modulate NF‐κB‐ and ERS‐associated apoptosis in murine ventricular myocytes 87 . Cardiac apoptosis‐related lncRNA (CARL) is able to sponge miR‐539 in mice and thus indirectly upregulate its target PHB2, which modulates apoptosis and mitochondrial fission 88 .…”

The expression levels of plasma dimethylglycine (DMG), human maternally expressed gene 3 (MEG3), and Apelin-12 in patients with acute myocardial infarction and their clinical significance

“…Previous research have showed that MEG3 modulates transient receptor potential cation channel subfamily V member 4 (TRPV4) expression to aggravate hypoxia-induced injury in rat cardiomyocytes by sponging miR-325-3p (9). MEG3 knockdown exerts cardioprotection by reducing endoplasmic reticulum stress (ERS)mediated apoptosis through targeting p53 post-myocardial infarction (10). MEG3 accelerates apoptosis of hypoxic myocardial cells via fork head box O1 (FoxO1) signaling pathway (11).…”