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N6-甲基腺苷 RNA 甲基化调控因子在急性心肌梗死诊断及亚型分类中的综合分析。

Comprehensive Analysis of N6-Methyladenosine RNA Methylation Regulators in the Diagnosis and Subtype Classification of Acute Myocardial Infarction.

机构信息

Department of Cardiology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan Province, China.

Henan Provincial Key Lab for Control of Coronary Heart Disease, Zhengzhou University Central China Fuwai Hospital, Zhengzhou, China.

出版信息

J Immunol Res. 2022 Aug 24;2022:5173761. doi: 10.1155/2022/5173761. eCollection 2022.

Abstract

Acute myocardial infarction (AMI) is still a huge danger to human health. Sensitive markers are necessary for the prediction of the risk of AMI and would be beneficial for managing the incidence rate. N6-methyladenosine (m6A) RNA methylation regulators have been confirmed to be involved in the development of various diseases. However, their function in AMI has not been fully elucidated. The purpose of this study was to determine the expression of m6A RNA methylation regulators in AMI as well as their possible functions and prognostic values. The GEO database was used to get the gene expression profiles of patients with and without AMI, and bioinformatics assays of genes with differently expressed expression were performed. We establish two separate m6A subtypes, and relationships between subtypes and immunity were studied. In this study, we identified IGF2BP1, FTO, RBM15, METTL3, YTHDC2, FMR1, and HNRNPA2B1 as the seven major m6A regulators. A nomogram model was developed and confirmed. The consensus clustering algorithm was conducted to categorize AMI patients into two m6A subtypes from the identified m6A regulators. Patients who have activated T-cell activities were found to be in clusterA; they may have a better prognosis as a result. Importantly, we found that patients with high METTL3 expressions had an increased level of Activated.CD4.T.cell and Type.2.T.helper.cell, while having a decreased level of CD56bright.natural.killer.cell, Macrophage, Monocyte, Natural.killer.cell, and Type.17.T.helper.cell. Overall, a diagnostic model of AMI was established based on the genes of IGF2BP1, FTO, RBM15, METTL3, YTHDC2, FMR1, and HNRNPA2B1. Our investigation of m6A subtypes may prove useful in the developments of therapy approaches for AMI.

摘要

急性心肌梗死(AMI)仍然是人类健康的巨大威胁。对于 AMI 风险的预测,需要敏感的标志物,这将有利于管理发病率。N6-甲基腺苷(m6A)RNA 甲基化调节剂已被证实参与各种疾病的发展。然而,它们在 AMI 中的作用尚未完全阐明。本研究旨在确定 m6A RNA 甲基化调节剂在 AMI 中的表达及其可能的功能和预后价值。我们使用 GEO 数据库获取 AMI 患者和非 AMI 患者的基因表达谱,并对表达差异的基因进行生物信息学分析。我们建立了两种独立的 m6A 亚型,并研究了亚型与免疫之间的关系。在这项研究中,我们确定了 IGF2BP1、FTO、RBM15、METTL3、YTHDC2、FMR1 和 HNRNPA2B1 作为七个主要的 m6A 调节剂。建立了列线图模型并进行了验证。采用共识聚类算法,根据鉴定出的 m6A 调节剂将 AMI 患者分为两种 m6A 亚型。发现激活 T 细胞活性的患者属于 clusterA;他们的预后可能更好。重要的是,我们发现高 METTL3 表达的患者的 Activated.CD4.T.cell 和 Type.2.T.helper.cell 水平升高,而 CD56bright.natural.killer.cell、Macrophage、Monocyte、Natural.killer.cell 和 Type.17.T.helper.cell 水平降低。总体而言,基于 IGF2BP1、FTO、RBM15、METTL3、YTHDC2、FMR1 和 HNRNPA2B1 的基因建立了 AMI 的诊断模型。我们对 m6A 亚型的研究可能有助于开发 AMI 的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e065/9433256/a41b0d656101/JIR2022-5173761.001.jpg

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