Long noncoding RNA MALAT1 promotes cardiomyocyte apoptosis after myocardial infarction via targeting miR-144-3p

Gong, Xiaohong; Zhu, Yun; Hai-xia, Chang; Li, Yongqin; Ma, Feng

doi:10.1042/bsr20191103

Cited by 50 publications

(40 citation statements)

References 23 publications

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“…We observed that miR-144 was highly abundant in MSC-derived exosomes in the present study. Consistent with other findings that miR-144 has antiapoptotic effects on CMCs in hypoxic conditions both in vitro and in vivo [17,35], we have demonstrated that miR-144 contained in MSC-derived exosomes protects CMCs from hypoxic injury by reducing cellapoptosis. MiR-144 mimics and a miR-144 inhibitor were used to further understand the anti-apoptotic functions of miR-144 in the present study.…”

Section: Discussionsupporting

confidence: 92%

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Wen¹,

Mai²,

Zhu³

et al. 2020

Stem Cell Res Ther

130

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Background: A growing body of evidence suggests that stem cell-derived exosomal microRNAs (miRNAs) could be a promising cardioprotective therapy in the context of hypoxic conditions. The present study aims to explore how miRNA-144 (miR-144), a miRNA contained in bone marrow mesenchymal stem cell (MSC)-derived exosomes, exerts a cardioprotective effect on cardiomyocyte apoptosis in the context of hypoxic conditions and identify the underlying mechanisms. Methods: MSCs were cultured using the whole bone marrow adherent method. MSC-derived exosomes were isolated using the total exosome isolation reagent and confirmed by nanoparticle trafficking analysis as well as western blotting using TSG101 and CD63 as markers. The hypoxic growth conditions for the H9C2 cells were established using the AnaeroPack method. Treatment conditions tested included H9C2 cells pre-incubated with exosomes, transfected with miR-144 mimics or inhibitor, or treated with the PTEN inhibitor SF1670, all under hypoxic growth conditions. Cell apoptosis was determined by flow cytometry using 7-ADD and Annexin V together. The expression levels of the miRNAs were detected by real-time PCR, and the expression levels of AKT/p-AKT, Bcl-2, caspase-3, HIF-1α, PTEN, and Rac-1 were measured by both real-time PCR and western blotting. Results: Exosomes were readily internalized by H9C2 cells after co-incubation for 12 h. Exosome-mediated protection of H9C2 cells from apoptosis was accompanied by increasing levels of p-AKT. MiR-144 was found to be highly enriched in MSC-derived exosomes. Transfection of cells with a miR-144 inhibitor weakened exosomemediated protection from apoptosis. Furthermore, treatment of cells grown in hypoxic conditions with miR-144 mimics resulted in decreased PTEN expression, increased p-AKT expression, and prevented H9C2 cell apoptosis, whereas treatment with a miR-144 inhibitor resulted in increased PTEN expression, decreased p-AKT expression, and enhanced H9C2 cell apoptosis in hypoxic conditions. We also validated that PTEN was a target of miR-144 by using luciferase reporter assay. Additionally, cells treated with SF1670, a PTEN-specific inhibitor, resulted in increased p-AKT expression and decreased H9C2 cell apoptosis. Conclusions: These findings demonstrate that MSC-derived exosomes inhibit cell apoptotic injury in hypoxic conditions by delivering miR-144 to cells, where it targets the PTEN/AKT pathway. MSC-derived exosomes could be a promising therapeutic vehicle to facilitate delivery of miRNA therapies to ameliorate ischemic conditions.

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Section: Discussionsupporting

confidence: 92%

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Wen¹,

Mai²,

Zhu³

et al. 2020

Stem Cell Res Ther

130

View full text Add to dashboard Cite

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“…MALAT1 was increased in serum of AMI and the serum MALAT1 might be used as the biomarker for AMI diagnosis . High expression of MALAT1 and low level of miR‐144 were found in myocardial tissue after myocardial infarction (MI) . And, MALAT1 was also induced by hypoxia and promoted mouse cardiomyocytes apoptosis via targeting miR‐144 .…”

Section: Malat1 and Cardiac Dysfunctionmentioning

confidence: 95%

“…24 And, MALAT1 was also induced by hypoxia and promoted mouse cardiomyocytes apoptosis via targeting miR-144. 24 Similarly, another study also showed that over-expression of MALAT1 promoted the H/R induced apoptosis of cardiomyocytes line HL-1 cell by sponging miR-145a. 21 MiR-145 could target adenovirus E1B-19 kDa-interacting protein 3, which plays a pivotal role in myocardial IR injury.…”

Section: Myocardial Ischemia Injurymentioning

confidence: 98%

“…In addition, MALAT1 also protected HCAECs against ox‐LDL induced apoptosis via sponging miR‐155 targeting suppressor of cytokine‐signaling‐1 (SOCS1) . In contrast, MALAT1 was found to promote the apoptosis of cardiomyocytes line HL‐1 or H9C2 under the H/R condition via sponging miR‐145a, miR‐144, or miR‐320 . MALAT1 promoted hypoxia‐induced apoptosis of myocardial cells by sponging miR‐200a‐3p, which targeted programmed cell death 4 (PDCD4) …”

Section: Malat1 and Pathophysiology Of Cvdsmentioning

confidence: 99%

“…High expression of MALAT1 and low level of miR‐144 were found in myocardial tissue after myocardial infarction (MI) . And, MALAT1 was also induced by hypoxia and promoted mouse cardiomyocytes apoptosis via targeting miR‐144 . Similarly, another study also showed that over‐expression of MALAT1 promoted the H/R induced apoptosis of cardiomyocytes line HL‐1 cell by sponging miR‐145a .…”

Section: Malat1 and Cardiac Dysfunctionmentioning

confidence: 99%

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The role of lncRNA MALAT1 in cardiovascular disease

Yan

Song

et al. 2019

IUBMB Life

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Cardiovascular disease (CVD) is the first leading cause of death worldwide. Understanding the molecular mechanism of signaling pathways involved in pathology of CVD is benefit for targeted therapeutics. Recently, long non‐coding RNAs (lncRNAs) are found and involved in regulation of pathology of CVD at different levels. Among them, MALAT1 attracted more attention as it was profoundly expressed in endothelial cells or cardiomyocytes in response to the risk factors of CVD, such as hypoxia, high glucose, cytokine, and oxidative stress. In this review, we summarize recent progresses in research on the molecular mechanism of MALAT1 on regulating the pathophysiological processes of CVD as well as its potential therapeutic applications.

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Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR‐206/ATG3 axis

Jing

Wang

Zhao

et al. 2021

J Biochem & Molecular Tox

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Previous studies have shown that propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague-Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)−206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot.Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3.Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.

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Long noncoding RNA MALAT1 promotes cardiomyocyte apoptosis after myocardial infarction via targeting miR-144-3p

Cited by 50 publications

References 23 publications

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

The role of lncRNA MALAT1 in cardiovascular disease

Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR‐206/ATG3 axis

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