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Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ

BACKGROUND: The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was inv...

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Autores principales: Zhang, Wen-Bin, Zheng, Yong-Fa, Wu, Yao-Gui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079209/
https://www.ncbi.nlm.nih.gov/pubmed/33986789
http://dx.doi.org/10.1155/2021/7595374
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author Zhang, Wen-Bin
Zheng, Yong-Fa
Wu, Yao-Gui
author_facet Zhang, Wen-Bin
Zheng, Yong-Fa
Wu, Yao-Gui
author_sort Zhang, Wen-Bin
collection PubMed
description BACKGROUND: The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was involved into the regulation of redox balance. However, the role of miR-128-3p in DOX-related cardiac injury remains not yet understood. The aim of this study was to investigate the biological effect of miR-128-3p in DOX-induced cardiotoxicity. METHODS: To induce DOX-related acute cardiac injury, mice were subjected to a single injection of DOX. Inhibition of myocardial miR-128-3p was achieved by an adeno-associated virus (AAV9) system carrying a miR-128-3p sponge. RESULTS: The data in our study indicated that miR-128-3p was upregulated in DOX-treated hearts and cardiomyocytes. Inhibition of miR-128-3p attenuated DOX-related cardiac injury and improved cardiac function in mice. Moreover, miR-128-3p inhibition could suppress myocardial inflammatory response, oxidative damage, and cell apoptotic death in DOX-treated mice. Further analysis showed that miR-128-3p could directly target peroxisome proliferator-activated receptor γ (PPAR-γ) and decrease PPAR-γ expression. Moreover, the protective effects provided by miR-128-3p inhibition were abolished by a PPAR-γ antagonist in vivo and in vitro. CONCLUSIONS: miR-128-3p inhibition attenuated DOX-related acute cardiac injury via the regulation of PPAR-γ in mice.
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spelling pubmed-80792092021-05-12 Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ Zhang, Wen-Bin Zheng, Yong-Fa Wu, Yao-Gui PPAR Res Research Article BACKGROUND: The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was involved into the regulation of redox balance. However, the role of miR-128-3p in DOX-related cardiac injury remains not yet understood. The aim of this study was to investigate the biological effect of miR-128-3p in DOX-induced cardiotoxicity. METHODS: To induce DOX-related acute cardiac injury, mice were subjected to a single injection of DOX. Inhibition of myocardial miR-128-3p was achieved by an adeno-associated virus (AAV9) system carrying a miR-128-3p sponge. RESULTS: The data in our study indicated that miR-128-3p was upregulated in DOX-treated hearts and cardiomyocytes. Inhibition of miR-128-3p attenuated DOX-related cardiac injury and improved cardiac function in mice. Moreover, miR-128-3p inhibition could suppress myocardial inflammatory response, oxidative damage, and cell apoptotic death in DOX-treated mice. Further analysis showed that miR-128-3p could directly target peroxisome proliferator-activated receptor γ (PPAR-γ) and decrease PPAR-γ expression. Moreover, the protective effects provided by miR-128-3p inhibition were abolished by a PPAR-γ antagonist in vivo and in vitro. CONCLUSIONS: miR-128-3p inhibition attenuated DOX-related acute cardiac injury via the regulation of PPAR-γ in mice. Hindawi 2021-04-20 /pmc/articles/PMC8079209/ /pubmed/33986789 http://dx.doi.org/10.1155/2021/7595374 Text en Copyright © 2021 Wen-Bin Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Wen-Bin
Zheng, Yong-Fa
Wu, Yao-Gui
Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title_full Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title_fullStr Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title_full_unstemmed Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title_short Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ
title_sort inhibition of mir-128-3p attenuated doxorubicin-triggered acute cardiac injury in mice by the regulation of ppar-γ
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079209/
https://www.ncbi.nlm.nih.gov/pubmed/33986789
http://dx.doi.org/10.1155/2021/7595374
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