The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity
Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on ca...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:e33b2b794dc84309859ac577334764272021-11-08T07:06:49ZThe Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity2297-055X10.3389/fcvm.2021.763469https://doaj.org/article/e33b2b794dc84309859ac577334764272021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.763469/fullhttps://doaj.org/toc/2297-055XCyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.Min ZhuMin ZhuYangong LiuYuanxiu SongShiqin ZhangChengwen HangFujian WuXianjuan LinZenghui HuangFeng LanFeng LanMing XuMing XuFrontiers Media S.A.articlecyclophosphamidecardiotoxicityJPH2m6A methylationMETTL3cardiomyocyteDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021) |
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cyclophosphamide cardiotoxicity JPH2 m6A methylation METTL3 cardiomyocyte Diseases of the circulatory (Cardiovascular) system RC666-701 |
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cyclophosphamide cardiotoxicity JPH2 m6A methylation METTL3 cardiomyocyte Diseases of the circulatory (Cardiovascular) system RC666-701 Min Zhu Min Zhu Yangong Liu Yuanxiu Song Shiqin Zhang Chengwen Hang Fujian Wu Xianjuan Lin Zenghui Huang Feng Lan Feng Lan Ming Xu Ming Xu The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| description |
Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity. |
| format |
article |
| author |
Min Zhu Min Zhu Yangong Liu Yuanxiu Song Shiqin Zhang Chengwen Hang Fujian Wu Xianjuan Lin Zenghui Huang Feng Lan Feng Lan Ming Xu Ming Xu |
| author_facet |
Min Zhu Min Zhu Yangong Liu Yuanxiu Song Shiqin Zhang Chengwen Hang Fujian Wu Xianjuan Lin Zenghui Huang Feng Lan Feng Lan Ming Xu Ming Xu |
| author_sort |
Min Zhu |
| title |
The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| title_short |
The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| title_full |
The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| title_fullStr |
The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| title_full_unstemmed |
The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity |
| title_sort |
role of mettl3-mediated n6-methyladenosine (m6a) of jph2 mrna in cyclophosphamide-induced cardiotoxicity |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/e33b2b794dc84309859ac57733476427 |
| work_keys_str_mv |
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