Long noncoding RNA Meg3 regulates cardiomyocyte apoptosis in myocardial infarction

Wu, Hongchun; Zhao, Zhen-Ao; Liu, Junwei; Hao, Kaili; You, Yu; Han, Xinglong; Li, Jingjing; Wang, Yixuan; Lei, Wei; Dong, Nianguo; Shen, Zhenya; Hu, Shijun

doi:10.1038/s41434-018-0045-4

Cited by 86 publications

(78 citation statements)

References 34 publications

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“…Current evidence has highlighted that lncRNA MEG3 was capable of targeting directly and activating p53 in various cell types . Consistent with these above reports, we identify that lncRNA MEG3 could directly bind to and regulate p53 expression in NMVMs by RIP and Western blot assays, but which were not entirely the same as Wu.et al research . Previous studies have found that p53 could also regulate the levels of GRP78, CHOP and Bax, which exerted key roles in the process of ERS, leading to apoptosis .…”

Section: Discussionsupporting

confidence: 90%

“…In order to further prove the functional link between ERS and p53, we detected the ERS-related protein levels in hypoxic NMVMs transfected with MEG3 after treatment with Pifithrin-α, a p53 inhibitor. In accord with a previous study, 28 we found that inhibition of p53 reduced lncRNA MEG3 levels in hypoxic NMVMs ( Figure S5A).…”

Section: Rna-binding Protein Immunoprecipitation (Rip) Assay Demonstrsupporting

confidence: 93%

“…The expression levels of lncRNA MEG3 were decreased by lentiviral delivery confirming that lncRNA MEG3 knockdown played a role in cardiac remodelling after MI. These improvements were observed in the EF and FS in lenti‐si lncRNA MEG3–treated animals by UCG, indicating improved cardiac function as a previous research showed . With regard to the parameters LVEDD and LVESD, a decline was noted at 1 week following MI, although the results were not statistically different most likely because of the relatively small number of animals used, which were not mentioned in Wu.et al research .…”

Section: Discussionmentioning

confidence: 53%

“…These improvements were observed in the EF and FS in lenti-si lncRNA MEG3-treated animals by UCG, indicating improved cardiac function as a previous research showed. 28 With regard to the parameters LVEDD and LVESD, a decline was noted at 1 week following MI, although the results were not statistically different most likely because of the relatively small number of animals used, which were not mentioned in Wu.et al research. 28 Some reasons for the difference with our data were most likely because of different dose of lentiviral and longer time for hypoxia in cardiomyocytes, leading to no significant change in p53 levels.…”

Section: Discussionmentioning

confidence: 78%

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

Zhao

Chen

et al. 2019

J Cellular Molecular Medi

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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‐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.

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Section: Discussionsupporting

confidence: 90%

Section: Rna-binding Protein Immunoprecipitation (Rip) Assay Demonstrsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 78%

See 2 more Smart Citations

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

Zhao

Chen

et al. 2019

J Cellular Molecular Medi

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“…LncRNAs have been demonstrated to regulate cardiac hypertrophy, mitochondrial function, cardiac fibrosis and apoptosis of cardiomyocyte . For example, the expression of Meg3 (maternally expressed gene 3) was up‐regulated in mouse injured heart after MI and involved in the regulation of apoptosis via binding to RNA‐binding protein FUS (fused in sarcoma) . However, detailed studies about lncRNAs’ role in regulating myocardial apoptosis are still limited.…”

Section: Introductionmentioning

confidence: 99%

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

Zhu

Zhuang

et al. 2019

J Cellular Molecular Medi

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Cardiomyocyte apoptosis is an important process occurred during cardiac ischaemia‐reperfusion injury. Long non‐coding RNAs (lncRNA) participate in the regulation of various cardiac diseases including ischaemic reperfusion (I/R) injury. In this study, we explored the potential role of lncRNA ACART (anti‐cardiomyocyte apoptosis‐related transcript) in cardiomyocyte injury and the underlying mechanism for the first time. We found that ACART was significantly down‐regulated in cardiac tissue of mice subjected to I/R injury or cultured cardiomyocytes treated with hydrogen peroxide (H2O2). Knockdown of ACART led to significant cardiomyocyte injury as indicated by reduced cell viability and increased apoptosis. In contrast, overexpression of ACART enhanced cell viability and reduced apoptosis of cardiomyocytes treated with H2O2. Meanwhile, ACART increased the expression of the B cell lymphoma 2 (Bcl‐2) and suppressed the expression of Bcl‐2‐associated X (Bax) and cytochrome‐C (Cyt‐C). In addition, PPAR‐γ was up‐regulated by ACART and inhibition of PPAR‐γ abolished the regulatory effects of ACART on cell apoptosis and the expression of Bcl‐2, Bax and Cyt‐C under H2O2 treatment. However, the activation of PPAR‐γ reversed the effects of ACART inhibition. The results demonstrate that ACART protects cardiomyocyte injury through modulating the expression of Bcl‐2, Bax and Cyt‐C, which is mediated by PPAR‐γ activation. These findings provide a new understanding of the role of lncRNA ACART in regulation of cardiac I/R injury.

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Retracted: Long noncoding RNA MEG3 deteriorates inflammatory damage by downregulating microRNA‐101a

Tang

Han

Jiang

et al. 2019

J of Cellular Biochemistry

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Valvulopathy is a familiar heart disease, which fearfully harms the health of the body. We studied the effects and mechanism of long noncoding RNA maternally expressed gene 3 (lncMEG3) on MVICs cell in inflammatory damage. Cell Counting Kit‐8 and flow cytometry were respectively used to detect the effect of tumor necrosis factor α (TNF‐α), MEG3 and microRNA (miR)‐101a on cell viability and apoptosis. Moreover, MEG3 and miR‐101a expression were changed by cell transfection and investigated by reverse transcription‐quantitative polymerase chain reaction. Furthermore, Western blot was used to investigate the levels of Bax, pro‐caspase‐3, cleaved‐caspase‐3, pro‐caspase‐9, cleaved‐caspase‐9, interleukin (IL)‐1β, IL‐6 and related‐proteins of cell pathways. Otherwise, the levels of IL‐1β and IL‐6 were also investigated by enzyme‐linked immunosorbent assay kit. Reactive oxygen species (ROS) was examined by ROS assay. We found TNF‐α caused inflammatory damage and upregulated MEG3. MEG3 was overexpressed and silenced in cells. Besides, MEG3 deteriorated inflammatory damage. Furthermore, MEG3 negatively regulated miR‐101a and miR‐101a mimic could reverse the effect of pc‐MEG3. Besides, MEG3 enhanced the JNK and NF‐κB pathways by downregulating miR‐101a. In conclusion, MEG3 deteriorated cell inflammatory damage by downregulating miR‐101a via JNK and NF‐κB pathways.

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Long noncoding RNA Meg3 regulates cardiomyocyte apoptosis in myocardial infarction

Cited by 86 publications

References 34 publications

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

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

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

Retracted: Long noncoding RNA MEG3 deteriorates inflammatory damage by downregulating microRNA‐101a

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