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Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells

Doxorubicin (Dox) is a widely used powerful chemotherapeutic component for cancer treatment. However, its clinical application has been hampered due to doxorubicin-induced cardiomyopathy upon the cessation of chemotherapy. Previous studies revealed that PPARγ plays a crucial protective role in cardi...

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Autores principales: Pakravan, Golnaz, Foroughmand, Ali Mohammad, Peymani, Maryam, Ghaedi, Kamran, Hashemi, Motahare-Sadat, Hajjari, Mohammadreza, Nasr-Esfahani, Mohammad Hossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037713/
https://www.ncbi.nlm.nih.gov/pubmed/29988029
http://dx.doi.org/10.1038/s41419-018-0797-1
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author Pakravan, Golnaz
Foroughmand, Ali Mohammad
Peymani, Maryam
Ghaedi, Kamran
Hashemi, Motahare-Sadat
Hajjari, Mohammadreza
Nasr-Esfahani, Mohammad Hossein
author_facet Pakravan, Golnaz
Foroughmand, Ali Mohammad
Peymani, Maryam
Ghaedi, Kamran
Hashemi, Motahare-Sadat
Hajjari, Mohammadreza
Nasr-Esfahani, Mohammad Hossein
author_sort Pakravan, Golnaz
collection PubMed
description Doxorubicin (Dox) is a widely used powerful chemotherapeutic component for cancer treatment. However, its clinical application has been hampered due to doxorubicin-induced cardiomyopathy upon the cessation of chemotherapy. Previous studies revealed that PPARγ plays a crucial protective role in cardiomyocytes. Modulation of miRNA expression is an applicable approach for prohibition of toxicity induction. Therefore, the aim of present study is uprising of PPARγ transcript levels via manipulation of miRNAs to limit Dox-induced cardiotoxicity in mESCs-derived cardiac cells, as in vitro model cell to provide a simple direct approach for further clinical therapies. Based on bioinformatics data mining, eventually miR-130a was selected to target PPARγ. This miRNA is highly expressed in heart. The expression of miR-130a increases sharply upon Dox treatment while specific antagomiR-130a reverses Dox-induced reduced expression of PPARγ, cellular apoptosis, and inflammation. Our data strongly suggest that antagomiR-130a limits Dox-induced cellular toxicity via PPARγ upregulation and may have clinical relevance to limit in vivo Dox toxicity.
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spelling pubmed-60377132018-07-11 Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells Pakravan, Golnaz Foroughmand, Ali Mohammad Peymani, Maryam Ghaedi, Kamran Hashemi, Motahare-Sadat Hajjari, Mohammadreza Nasr-Esfahani, Mohammad Hossein Cell Death Dis Article Doxorubicin (Dox) is a widely used powerful chemotherapeutic component for cancer treatment. However, its clinical application has been hampered due to doxorubicin-induced cardiomyopathy upon the cessation of chemotherapy. Previous studies revealed that PPARγ plays a crucial protective role in cardiomyocytes. Modulation of miRNA expression is an applicable approach for prohibition of toxicity induction. Therefore, the aim of present study is uprising of PPARγ transcript levels via manipulation of miRNAs to limit Dox-induced cardiotoxicity in mESCs-derived cardiac cells, as in vitro model cell to provide a simple direct approach for further clinical therapies. Based on bioinformatics data mining, eventually miR-130a was selected to target PPARγ. This miRNA is highly expressed in heart. The expression of miR-130a increases sharply upon Dox treatment while specific antagomiR-130a reverses Dox-induced reduced expression of PPARγ, cellular apoptosis, and inflammation. Our data strongly suggest that antagomiR-130a limits Dox-induced cellular toxicity via PPARγ upregulation and may have clinical relevance to limit in vivo Dox toxicity. Nature Publishing Group UK 2018-07-09 /pmc/articles/PMC6037713/ /pubmed/29988029 http://dx.doi.org/10.1038/s41419-018-0797-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pakravan, Golnaz
Foroughmand, Ali Mohammad
Peymani, Maryam
Ghaedi, Kamran
Hashemi, Motahare-Sadat
Hajjari, Mohammadreza
Nasr-Esfahani, Mohammad Hossein
Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title_full Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title_fullStr Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title_full_unstemmed Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title_short Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells
title_sort downregulation of mir-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the pparγ expression in mescs-derived cardiac cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037713/
https://www.ncbi.nlm.nih.gov/pubmed/29988029
http://dx.doi.org/10.1038/s41419-018-0797-1
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