Long-noncoding RNA MALAT1 sponges microRNA-92a-3p to inhibit doxorubicin-induced cardiac senescence by targeting ATG4a

Xia, Wenzheng; Chen, Hanbin; Xie, Congying; Hou, Meng

doi:10.18632/aging.103136

Cited by 65 publications

(61 citation statements)

References 70 publications

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“…Previous studies have shown that eliminate or reduce the cardiotoxicity of DOX and improve its curative effect is still an unsolved and prominent problem [29][30][31][32][33][34]. Furthermore, among six cardiomyocyte death forms (apoptosis, autophagy, necrosis, necroptosis, pyroptosis, and ferroptosis), accumulating evidences suggest an emerging role of pyroptosis in DOX-induced cardiomyopathy [5].…”

Section: Discussionmentioning

confidence: 99%

HSPB1 Promotes Doxorubicin-induced Cardiomyocyte Pyroptosis by Inhibiting AATF

Tang

Liu

et al. 2021

Preprint

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Background: Doxorubicin (DOX) has been widely used for the treatment of different kinds of cancers. However, the adverse effects, especially cardiotoxicity, which limit the long-term use of DOX. Although some signaling pathways have been investigated to be participated in DOX-induced cardiotoxicity, however, the mechanisms underlying DOX-induced cardiotoxicity need to be further investigated. Recent study suggested that heat shock proteins (HSPs) play a role in cell apoptosis and pyroptosis. However, we do not know yet whether heat shock protein beta-1 (HSPB1), a member of HSPs family, is involved in DOX-induced cardiomyocyte pyroptosis. This study aimed to evaluate the effects of HSPB1 and apoptosis antagonizing transcription factor (AATF) in DOX-induced pyroptosis in cardiomycytes.Results: We found that DOX remarkably enhanced the expression of HSPB1 but reduces AATF expression in cardiomyocytes. We also found that either inhibition of HSPB1 by small interfering RNA (siRNA) or overexpression of AATF by transfection of AATF plasmid significantly attenuated DOX-induced cardiomyocyte pyroptosis. Moreover, HSPB1 interacts with AATF. Furthermore, inhibition of HSPB1 and AATF restores the DOX-induced cardiomyocyte pyroptosis. Conclusion: Our findings reveal a novel pathway that cardiomyocyte pyroptosis is regulated through HSPB1-AATF-caspase-3-GSDME pathway following DOX treatment, suggesting that HSPB1-AATF-dependent pyroptosis may provide a novel therapeutic strategy to reduce cardiotoxicity induced by DOX.

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Section: Discussionmentioning

confidence: 99%

HSPB1 Promotes Doxorubicin-induced Cardiomyocyte Pyroptosis by Inhibiting AATF

Tang

Liu

et al. 2021

Preprint

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“…As is mentioned above, exosomes generated from MSCs could inhibit DOX-induced cardiac senescence, this cardioprotective effect was mediated by overexpressing lncRNA MALAT1 in exosome Hypoxia . In detail, MALAT1 sponged microRNA-92a-3p, and the binding of them activated ATG4a , improving mitochondrial metabolism and thus partially playing a cardioprotective role in DOX-induced cardiac lesions 71 .…”

Section: Exosomes As Therapeutic Delivery Vehiclesmentioning

confidence: 98%

“…Moreover, hypoxia, used to be considered as a detrimental factor for it can induce ischemia-reperfusion (I/R) injury, has also intriguingly improved biological activity and showed better therapeutic functions. For instance, human adipose-derived mesenchymal stem cells (AT-MSCs) were treated with hypoxia and stimulated the secretion of exosome Hypoxia , exosome Hypoxia showed superiority in protecting cardiomyocytes from senescence induced by DOX 71 . The indistinguishably therapeutic effects of AT-MSC and BM-MSC implied that the secretion of exosomes was the common characteristic of MSCs, and the pretreatment of hypoxia could achieve better effects.…”

Section: Exosomes As Therapeutic Delivery Vehiclesmentioning

confidence: 99%

Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity

et al. 2021

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Doxorubicin (DOX) is a kind of representative anthracyclines. It has greatly prolonged lifespan of cancer patients. However, a long course of DOX chemotherapy could induce various forms of deaths of cardiomyocytes, such as apoptosis, pyroptosis and ferroptosis, contributing to varieties of cardiac complications called cardiotoxicity. It has become a major concern considering the large number of cancer patients' worldwide and increased survival rates after chemotherapy. Exosomes, a subgroup of extracellular vesicles (EVs), are secreted by nearly all cells and consist of lipid bilayers, nucleic acids and proteins. They can serve as mediators between intercellular communication via the transfer of bioactive molecules from secretory to recipient cells, modulating multiple pathophysiological processes. It has been proven that exosomes in body fluids can serve as biomarkers for doxorubicin-induced cardiotoxicity (DIC). Moreover, exosomes have attracted considerable attention because of their capacity as carriers of certain proteins, genetic materials (miRNA and lncRNA), and chemotherapeutic drugs to decrease the dosage of DOX and alleviate cardiotoxicity. This review briefly describes the characteristics of exosomes and highlights their clinical application potential as diagnostic biomarkers and drug delivery vehicles for DIC, thus providing a strategy for addressing it based on exosomes.

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“…In addition, hypoxic MSCs-exos can improve myocardial cell metabolism disorders. Database and luciferase reporter assays show that hypoxia-induced ADMSCs-exo- MALAT1 can improve mitochondrial dysfunction in cardiomyocytes after Dox treatment by targeting MIR-92a-3p / ATG4A and combating cardiac aging ( 47 ). In addition, Zhuang et al found that the lncRNA NEAT1 was significantly enriched in exosomes derived from BMSCs treated with MIF.…”

Section: Cardiac Agingmentioning

confidence: 99%

New Developments in Exosomal lncRNAs in Cardiovascular Diseases

Yuan

Huang

2021

Front. Cardiovasc. Med.

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Long non-coding RNAs (lncRNAs) are non-coding RNAs with lengths >200 nt and are involved in the occurrence and development of cardiovascular diseases (CVDs). Exosomes are secreted and produced by various cell types. Exosome contents include various ncRNAs, proteins and lipids. Exosomes are also important mediators of intercellular communication. The proportion of lncRNAs in exosomes is low, but increasing evidence suggests that exosomal lncRNAs play important roles in CVDs. We focused on research progress in exosomal lncRNAs in atherosclerosis, myocardial infarction, myocardial ischemia-reperfusion injury, cardiac angiogenesis, cardiac aging, rheumatic heart disease, and chronic kidney disease combined with CVD. The potential diagnostic and therapeutic effects of exosomal lncRNAs in CVDs are summarized based on preclinical studies involving animal and cell models and circulating exosomes in clinical patients. Finally, the challenges and possible prospects of exosomes and exosomal lncRNAs in clinical applications related to CVD are discussed.

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Long-noncoding RNA MALAT1 sponges microRNA-92a-3p to inhibit doxorubicin-induced cardiac senescence by targeting ATG4a

Cited by 65 publications

References 70 publications

HSPB1 Promotes Doxorubicin-induced Cardiomyocyte Pyroptosis by Inhibiting AATF

HSPB1 Promotes Doxorubicin-induced Cardiomyocyte Pyroptosis by Inhibiting AATF

Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity

New Developments in Exosomal lncRNAs in Cardiovascular Diseases

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