LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis
Ferroptosis is associated with the pathology of myocardial ischemia/reperfusion (MI/R) injury following myocardial infarction, which is a leading cause of death worldwide. Although long noncoding RNAs (lncRNAs) are known to regulate gene expression, their roles in MI/R-induced ferroptosis remain unc...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.672391/full |
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| author | Weixin Sun Weixin Sun Weixin Sun Weixin Sun Xiang Wu Xiang Wu Xiang Wu Peng Yu Peng Yu Qian Zhang Qian Zhang Le Shen Le Shen Jiandong Chen Jiandong Chen Huaqin Tong Huaqin Tong Huaqin Tong Manlu Fan Manlu Fan Manlu Fan Haibo Shi Haibo Shi Haibo Shi Xiaohu Chen Xiaohu Chen |
| author_facet | Weixin Sun Weixin Sun Weixin Sun Weixin Sun Xiang Wu Xiang Wu Xiang Wu Peng Yu Peng Yu Qian Zhang Qian Zhang Le Shen Le Shen Jiandong Chen Jiandong Chen Huaqin Tong Huaqin Tong Huaqin Tong Manlu Fan Manlu Fan Manlu Fan Haibo Shi Haibo Shi Haibo Shi Xiaohu Chen Xiaohu Chen |
| author_sort | Weixin Sun |
| collection | DOAJ |
| description | Ferroptosis is associated with the pathology of myocardial ischemia/reperfusion (MI/R) injury following myocardial infarction, which is a leading cause of death worldwide. Although long noncoding RNAs (lncRNAs) are known to regulate gene expression, their roles in MI/R-induced ferroptosis remain unclear. In this study, we explored the lncRNA expression profiles in a rat model of MI/R injury and found that the novel lncRNA, lncAABR07025387.1, was highly expressed in MI/R-injured myocardial tissues and hypoxia/reoxygenation (H/R)-challenged myocardial cells. Silencing lncAABR07025387.1 improved MI/R injury in vivo and inhibited myocardial cell ferroptosis under H/R conditions. Bioinformatics analyses and luciferase, pull-down, and RNA-binding immunoprecipitation assays further revealed that lncAABR07025387.1 interacted with miR-205, which directly targeted ACSL4, a known contributor to ferroptosis. Furthermore, downregulating miR-205 reversed the ACSL4 inhibition induced by silencing lncAABR07025387.1. These findings suggest that, mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. In conclusion, this study demonstrates that lncAABR07025387.1 acts as a competing endogenous RNA during MI/R injury and highlights the therapeutic potential of lncRNAs for treating myocardial injury. |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T16:21:38Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-e3ac23d22f7c4e85848aab00acfd88eb2022-12-22T04:14:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-011010.3389/fcell.2022.672391672391LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated FerroptosisWeixin Sun0Weixin Sun1Weixin Sun2Weixin Sun3Xiang Wu4Xiang Wu5Xiang Wu6Peng Yu7Peng Yu8Qian Zhang9Qian Zhang10Le Shen11Le Shen12Jiandong Chen13Jiandong Chen14Huaqin Tong15Huaqin Tong16Huaqin Tong17Manlu Fan18Manlu Fan19Manlu Fan20Haibo Shi21Haibo Shi22Haibo Shi23Xiaohu Chen24Xiaohu Chen25Department of Cardiology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Gerontology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Gerontology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Liyang City Hospital of TCM, Changzhou, ChinaDepartment of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaFerroptosis is associated with the pathology of myocardial ischemia/reperfusion (MI/R) injury following myocardial infarction, which is a leading cause of death worldwide. Although long noncoding RNAs (lncRNAs) are known to regulate gene expression, their roles in MI/R-induced ferroptosis remain unclear. In this study, we explored the lncRNA expression profiles in a rat model of MI/R injury and found that the novel lncRNA, lncAABR07025387.1, was highly expressed in MI/R-injured myocardial tissues and hypoxia/reoxygenation (H/R)-challenged myocardial cells. Silencing lncAABR07025387.1 improved MI/R injury in vivo and inhibited myocardial cell ferroptosis under H/R conditions. Bioinformatics analyses and luciferase, pull-down, and RNA-binding immunoprecipitation assays further revealed that lncAABR07025387.1 interacted with miR-205, which directly targeted ACSL4, a known contributor to ferroptosis. Furthermore, downregulating miR-205 reversed the ACSL4 inhibition induced by silencing lncAABR07025387.1. These findings suggest that, mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. In conclusion, this study demonstrates that lncAABR07025387.1 acts as a competing endogenous RNA during MI/R injury and highlights the therapeutic potential of lncRNAs for treating myocardial injury.https://www.frontiersin.org/articles/10.3389/fcell.2022.672391/fullmyocardial I/R injuryferroptosismiR-205ACSL4lncAABR07025387.1 |
| spellingShingle | Weixin Sun Weixin Sun Weixin Sun Weixin Sun Xiang Wu Xiang Wu Xiang Wu Peng Yu Peng Yu Qian Zhang Qian Zhang Le Shen Le Shen Jiandong Chen Jiandong Chen Huaqin Tong Huaqin Tong Huaqin Tong Manlu Fan Manlu Fan Manlu Fan Haibo Shi Haibo Shi Haibo Shi Xiaohu Chen Xiaohu Chen LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis Frontiers in Cell and Developmental Biology myocardial I/R injury ferroptosis miR-205 ACSL4 lncAABR07025387.1 |
| title | LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis |
| title_full | LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis |
| title_fullStr | LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis |
| title_full_unstemmed | LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis |
| title_short | LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis |
| title_sort | lncaabr07025387 1 enhances myocardial ischemia reperfusion injury via mir 205 acsl4 mediated ferroptosis |
| topic | myocardial I/R injury ferroptosis miR-205 ACSL4 lncAABR07025387.1 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.672391/full |
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