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miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury
Ferroptosis is a form of cell death induced by excess iron and accumulation of reactive oxygen species in cells. Recently, ferroptosis has been reported to be associated with cancer and ischemia/reperfusion (I/R) injury in multiple organs. However, the regulatory effects and underlying mechanisms of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414249/ https://www.ncbi.nlm.nih.gov/pubmed/34485394 http://dx.doi.org/10.3389/fcvm.2021.663832 |
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author | Sun, Weixin Shi, Ruijie Guo, Jun Wang, Haiyan Shen, Le Shi, Haibo Yu, Peng Chen, Xiaohu |
author_facet | Sun, Weixin Shi, Ruijie Guo, Jun Wang, Haiyan Shen, Le Shi, Haibo Yu, Peng Chen, Xiaohu |
author_sort | Sun, Weixin |
collection | PubMed |
description | Ferroptosis is a form of cell death induced by excess iron and accumulation of reactive oxygen species in cells. Recently, ferroptosis has been reported to be associated with cancer and ischemia/reperfusion (I/R) injury in multiple organs. However, the regulatory effects and underlying mechanisms of myocardial I/R injury are not well-understood. The role of miR-135b-3p as an oncogene that accelerates tumor development has been confirmed; however, its role in myocardial I/R is not fully understood. In this study, we established an in vivo myocardial I/R rat model and an in vitro hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocyte injury model and observed that ferroptosis occurred in tissues and cells during I/R myocardial injury. We used database analysis to find miR-135b-3p and validated its inhibitory effect on the ferroptosis-related gene glutathione peroxidase 4 (Gpx4), using a luciferase reporter assay. Furthermore, miR-135b-3p was found to promote the myocardial I/R injury by downregulating GPX4 expression. The results of this study elucidate a novel function of miR-135b-3p in exacerbating cardiomyocyte ferroptosis, providing a new therapeutic target for improving I/R injury. |
format | Online Article Text |
id | pubmed-8414249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84142492021-09-04 miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury Sun, Weixin Shi, Ruijie Guo, Jun Wang, Haiyan Shen, Le Shi, Haibo Yu, Peng Chen, Xiaohu Front Cardiovasc Med Cardiovascular Medicine Ferroptosis is a form of cell death induced by excess iron and accumulation of reactive oxygen species in cells. Recently, ferroptosis has been reported to be associated with cancer and ischemia/reperfusion (I/R) injury in multiple organs. However, the regulatory effects and underlying mechanisms of myocardial I/R injury are not well-understood. The role of miR-135b-3p as an oncogene that accelerates tumor development has been confirmed; however, its role in myocardial I/R is not fully understood. In this study, we established an in vivo myocardial I/R rat model and an in vitro hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocyte injury model and observed that ferroptosis occurred in tissues and cells during I/R myocardial injury. We used database analysis to find miR-135b-3p and validated its inhibitory effect on the ferroptosis-related gene glutathione peroxidase 4 (Gpx4), using a luciferase reporter assay. Furthermore, miR-135b-3p was found to promote the myocardial I/R injury by downregulating GPX4 expression. The results of this study elucidate a novel function of miR-135b-3p in exacerbating cardiomyocyte ferroptosis, providing a new therapeutic target for improving I/R injury. Frontiers Media S.A. 2021-08-13 /pmc/articles/PMC8414249/ /pubmed/34485394 http://dx.doi.org/10.3389/fcvm.2021.663832 Text en Copyright © 2021 Sun, Shi, Guo, Wang, Shen, Shi, Yu and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Sun, Weixin Shi, Ruijie Guo, Jun Wang, Haiyan Shen, Le Shi, Haibo Yu, Peng Chen, Xiaohu miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title | miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title_full | miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title_fullStr | miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title_full_unstemmed | miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title_short | miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury |
title_sort | mir-135b-3p promotes cardiomyocyte ferroptosis by targeting gpx4 and aggravates myocardial ischemia/reperfusion injury |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414249/ https://www.ncbi.nlm.nih.gov/pubmed/34485394 http://dx.doi.org/10.3389/fcvm.2021.663832 |
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