PMID- 37041267 OWN - NLM STAT- MEDLINE DCOM- 20230414 LR - 20230426 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Apr 11 TI - m6A regulator-mediated RNA methylation modification patterns are involved in the regulation of the immune microenvironment in ischaemic cardiomyopathy. PG - 5904 LID - 10.1038/s41598-023-32919-4 [doi] LID - 5904 AB - The role of RNA N6-methyladenosine (m6A) modification in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains largely unclear. This study first identified differential m6A regulators between ICM and healthy samples, and then systematically evaluated the effects of m6A modification on the characteristics of the immune microenvironment in ICM, including the infiltration of immune cells, the human leukocyte antigen (HLA) gene, and HALLMARKS pathways. A total of seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were identified using a random forest classifier. A diagnostic nomogram based on these seven key m6A regulators could effectively distinguish patients with ICM from healthy subjects. We further identified two distinct m6A modification patterns (m6A cluster-A and m6A cluster-B) that are mediated by these seven regulators. Meanwhile, we also noted that one m6A regulator, WTAP, was gradually upregulated, while the others were gradually downregulated in the m6A cluster-A vs. m6A cluster-B vs. healthy subjects. In addition, we observed that the degree of infiltration of the activated dendritic cells, macrophages, natural killer (NK) T cells, and type-17 T helper (Th17) cells gradually increased in m6A cluster-A vs. m6A cluster-B vs. healthy subjects. Furthermore, m6A regulators, including FTO, YTHDC1, YTHDF3, FMR1, ZC3H13, and RBM15 were significantly negatively correlated with the above-mentioned immune cells. Additionally, several differential HLA genes and HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. These results suggest that m6A modification plays a key role in the complexity and diversity of the immune microenvironment in ICM, and seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15, and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop immunotherapy strategies with a higher level of accuracy for patients with a significant immune response. CI - (c) 2023. The Author(s). FAU - Zheng, Peng-Fei AU - Zheng PF AD - Cardiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, ChangshaHunan, 410000, China. AD - Clinical Research Center for Heart Failure in Hunan Province, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. AD - Epidemiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. FAU - Hong, Xiu-Qin AU - Hong XQ AD - Clinical Research Center for Heart Failure in Hunan Province, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. AD - Epidemiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. FAU - Liu, Zheng-Yu AU - Liu ZY AD - Cardiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, ChangshaHunan, 410000, China. AD - Clinical Research Center for Heart Failure in Hunan Province, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. AD - Epidemiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. FAU - Zheng, Zhao-Fen AU - Zheng ZF AD - Cardiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, ChangshaHunan, 410000, China. AD - Clinical Research Center for Heart Failure in Hunan Province, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. AD - Epidemiology Department, Hunan Provincial People's Hospital, No. 61 West Jiefang Road, Furong District, Changsha, 410000, Hunan, China. FAU - Liu, Peng AU - Liu P AUID- ORCID: 0000-0002-3095-0352 AD - Department of Cardiology, The Central Hospital of ShaoYang, No. 36 QianYuan Lane, Daxiang District, Shaoyang, 422000, Hunan, China. ying_lpxm@163.com. FAU - Chen, Lu-Zhu AU - Chen LZ AUID- ORCID: 0000-0001-8206-8153 AD - Department of Cardiology, The Central Hospital of ShaoYang, No. 36 QianYuan Lane, Daxiang District, Shaoyang, 422000, Hunan, China. luzhuchen@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230411 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - K72T3FS567 (Adenosine) RN - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO) RN - 0 (FMR1 protein, human) RN - 139135-51-6 (Fragile X Mental Retardation Protein) RN - EC 1.14.11.33 (FTO protein, human) RN - 63231-63-0 (RNA) RN - 0 (GPM6A protein, human) SB - IM MH - Humans MH - Adenosine MH - Alpha-Ketoglutarate-Dependent Dioxygenase FTO MH - *Cardiomyopathies MH - Fragile X Mental Retardation Protein MH - Methylation MH - *Myocardial Ischemia MH - RNA PMC - PMC10090050 COIS- The authors declare no competing interests. EDAT- 2023/04/12 06:00 MHDA- 2023/04/13 06:43 PMCR- 2023/04/11 CRDT- 2023/04/11 23:22 PHST- 2022/11/11 00:00 [received] PHST- 2023/04/04 00:00 [accepted] PHST- 2023/04/13 06:43 [medline] PHST- 2023/04/11 23:22 [entrez] PHST- 2023/04/12 06:00 [pubmed] PHST- 2023/04/11 00:00 [pmc-release] AID - 10.1038/s41598-023-32919-4 [pii] AID - 32919 [pii] AID - 10.1038/s41598-023-32919-4 [doi] PST - epublish SO - Sci Rep. 2023 Apr 11;13(1):5904. doi: 10.1038/s41598-023-32919-4.