Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance
Abstract Background Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. Methods After RNA isolation, the...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-023-01602-w |
| _version_ | 1827581579775442944 |
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| author | Ruoyan Yu Qinglin Yu Zhenwei Li Jiyi Li Jin Yang Yingchu Hu Nan Zheng Xiaojin Li Yudie Song Jiahui Li Xiaomin Chen Weiping Du Jia Su |
| author_facet | Ruoyan Yu Qinglin Yu Zhenwei Li Jiyi Li Jin Yang Yingchu Hu Nan Zheng Xiaojin Li Yudie Song Jiahui Li Xiaomin Chen Weiping Du Jia Su |
| author_sort | Ruoyan Yu |
| collection | DOAJ |
| description | Abstract Background Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. Methods After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR. Results The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients. Conclusion The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future. |
| first_indexed | 2024-03-08T22:37:23Z |
| format | Article |
| id | doaj.art-726bc53dc5a240bcbd9fd0839e0aa0d4 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-08T22:37:23Z |
| publishDate | 2023-12-01 |
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| series | Clinical Epigenetics |
| spelling | doaj.art-726bc53dc5a240bcbd9fd0839e0aa0d42023-12-17T12:21:05ZengBMCClinical Epigenetics1868-70832023-12-0115111910.1186/s13148-023-01602-wTranscriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistanceRuoyan Yu0Qinglin Yu1Zhenwei Li2Jiyi Li3Jin Yang4Yingchu Hu5Nan Zheng6Xiaojin Li7Yudie Song8Jiahui Li9Xiaomin Chen10Weiping Du11Jia Su12Department of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Traditional Chinese Internal Medicine, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, Yuyao People’s Hospital of Zhejiang ProvinceDepartment of Geriatrics, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, HwaMei Hospital, University of Chinese Academy of SciencesDepartment of Geriatrics, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityDepartment of Cardiology, The First Affiliated Hospital of Ningbo UniversityAbstract Background Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. Methods After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR. Results The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients. Conclusion The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.https://doi.org/10.1186/s13148-023-01602-wm6A modificationClopidogrel resistanceCoronary artery diseaseRNA transcriptome expression |
| spellingShingle | Ruoyan Yu Qinglin Yu Zhenwei Li Jiyi Li Jin Yang Yingchu Hu Nan Zheng Xiaojin Li Yudie Song Jiahui Li Xiaomin Chen Weiping Du Jia Su Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance Clinical Epigenetics m6A modification Clopidogrel resistance Coronary artery disease RNA transcriptome expression |
| title | Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance |
| title_full | Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance |
| title_fullStr | Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance |
| title_full_unstemmed | Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance |
| title_short | Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance |
| title_sort | transcriptome wide map of n6 methyladenosine m6a profiling in coronary artery disease cad with clopidogrel resistance |
| topic | m6A modification Clopidogrel resistance Coronary artery disease RNA transcriptome expression |
| url | https://doi.org/10.1186/s13148-023-01602-w |
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