Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction
ObjectiveAcute myocardial infarction (AMI) is a severe cardiovascular disease that threatens human life and health globally. N6-methyladenosine (m6A) governs the fate of RNAs via m6A regulators. Nevertheless, how m6A regulators affect AMI remains to be deciphered. To solve this issue, an integrative...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308978/full |
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| author | Peng Chao Peng Chao Xueqin Zhang Lei Zhang Yong Wang Miriban Wusiman Gulizere Aimaijiang Xiaoyang Chen Yining Yang Yining Yang |
| author_facet | Peng Chao Peng Chao Xueqin Zhang Lei Zhang Yong Wang Miriban Wusiman Gulizere Aimaijiang Xiaoyang Chen Yining Yang Yining Yang |
| author_sort | Peng Chao |
| collection | DOAJ |
| description | ObjectiveAcute myocardial infarction (AMI) is a severe cardiovascular disease that threatens human life and health globally. N6-methyladenosine (m6A) governs the fate of RNAs via m6A regulators. Nevertheless, how m6A regulators affect AMI remains to be deciphered. To solve this issue, an integrative analysis of m6A regulators in AMI was conducted.MethodsWe acquired transcriptome profiles (GSE59867, GSE48060) of peripheral blood samples from AMI patients and healthy controls. Key m6A regulators were used for LASSO, and consensus clustering was conducted. Next, the m6A score was also computed. Immune cell infiltration, ferroptosis, and oxidative stress were evaluated. In-vitro and in-vivo experiments were conducted to verify the role of the m6A regulator ALKBH5 in AMI.ResultsMost m6A regulators presented notable expression alterations in circulating cells of AMI patients versus those of controls. Based on key m6A regulators, we established a gene signature and a nomogram for AMI diagnosis and risk prediction. AMI patients were classified into three m6A clusters or gene clusters, respectively, and each cluster possessed the unique properties of m6A modification, immune cell infiltration, ferroptosis, and oxidative stress. Finally, the m6A score was utilized to quantify m6A modification patterns. Therapeutic targeting of ALKBH5 greatly alleviated apoptosis and intracellular ROS in H/R-induced H9C2 cells and NRCMs.ConclusionAltogether, our findings highlight the clinical significance of m6A regulators in the diagnosis and risk prediction of AMI and indicate the critical roles of m6A modification in the regulation of immune cell infiltration, ferroptosis, and oxidative stress. |
| first_indexed | 2024-04-24T22:23:28Z |
| format | Article |
| id | doaj.art-4fb6a2e6166a4305966ece506cade1d8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T22:23:28Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4fb6a2e6166a4305966ece506cade1d82024-03-20T04:32:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13089781308978Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarctionPeng Chao0Peng Chao1Xueqin Zhang2Lei Zhang3Yong Wang4Miriban Wusiman5Gulizere Aimaijiang6Xiaoyang Chen7Yining Yang8Yining Yang9Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaXinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Endocrinology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaXinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, Urumqi, Xinjiang Uygur Autonomous Region, ChinaObjectiveAcute myocardial infarction (AMI) is a severe cardiovascular disease that threatens human life and health globally. N6-methyladenosine (m6A) governs the fate of RNAs via m6A regulators. Nevertheless, how m6A regulators affect AMI remains to be deciphered. To solve this issue, an integrative analysis of m6A regulators in AMI was conducted.MethodsWe acquired transcriptome profiles (GSE59867, GSE48060) of peripheral blood samples from AMI patients and healthy controls. Key m6A regulators were used for LASSO, and consensus clustering was conducted. Next, the m6A score was also computed. Immune cell infiltration, ferroptosis, and oxidative stress were evaluated. In-vitro and in-vivo experiments were conducted to verify the role of the m6A regulator ALKBH5 in AMI.ResultsMost m6A regulators presented notable expression alterations in circulating cells of AMI patients versus those of controls. Based on key m6A regulators, we established a gene signature and a nomogram for AMI diagnosis and risk prediction. AMI patients were classified into three m6A clusters or gene clusters, respectively, and each cluster possessed the unique properties of m6A modification, immune cell infiltration, ferroptosis, and oxidative stress. Finally, the m6A score was utilized to quantify m6A modification patterns. Therapeutic targeting of ALKBH5 greatly alleviated apoptosis and intracellular ROS in H/R-induced H9C2 cells and NRCMs.ConclusionAltogether, our findings highlight the clinical significance of m6A regulators in the diagnosis and risk prediction of AMI and indicate the critical roles of m6A modification in the regulation of immune cell infiltration, ferroptosis, and oxidative stress.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308978/fullacute myocardial infarctionN6-methyladenosineimmune cell infiltrationferroptosisoxidative stressALKBH5 |
| spellingShingle | Peng Chao Peng Chao Xueqin Zhang Lei Zhang Yong Wang Miriban Wusiman Gulizere Aimaijiang Xiaoyang Chen Yining Yang Yining Yang Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction Frontiers in Immunology acute myocardial infarction N6-methyladenosine immune cell infiltration ferroptosis oxidative stress ALKBH5 |
| title | Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction |
| title_full | Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction |
| title_fullStr | Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction |
| title_full_unstemmed | Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction |
| title_short | Characterization of the m6A regulators’ landscape highlights the clinical significance of acute myocardial infarction |
| title_sort | characterization of the m6a regulators landscape highlights the clinical significance of acute myocardial infarction |
| topic | acute myocardial infarction N6-methyladenosine immune cell infiltration ferroptosis oxidative stress ALKBH5 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308978/full |
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