Correlation between methyltransferase METTL7B and atherosclerosis

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2025-07-31 DOI:10.1016/j.abb.2025.110560

Jian Xiong , Xiaoyun Peng , Liming Ma , Fangcheng Zhu , Yan Ding , Zhixiao Wang

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引用次数: 0

Abstract

Atherosclerosis (AS) is a serious threat to human health. Although glucose balance, lipid metabolism, inflammation and hypertension are closely related to AS, whether methyltransferase-like (METTL) family members are involved in the occurrence and development of AS remains elusive.

Differentially expressed genes of METTLs in AS and normal blood vessels in GSE43292 and GSE100927 databases were analyzed. Random forest screening was used to screen marker genes, and the intersection genes in the two databases were selected. GSE28829/GSE41571 and clinical tissue samples were used for verification. The databases were further used to analyze marker genes’ tissue and cellular localization and their correlation with lipid metabolism and efferocytosis.

7 and 17 differentially expressed METTL genes were obtained from GSE43292 and GSE100927 databases, respectively. METTL7B and METTL5 were verified as the intersection marker genes. Compared with the control group, the expression of METTL7B was significantly increased in advanced AS, AS ruptured plaque and clinical heavy-load plaque tissues. ROC curve analysis showed that the AUC of METTL7B in GSE28829 and GSE41571 was greater than 0.9. In addition, it was found that METTL7B was significantly correlated with lipid metabolism-related genes and promoted the formation of lipid droplets. METTL7B was positively correlated with atherosclerosis and macrophage-mediated efferocytosis. RNA-seq and targeted lipidomics results also confirmed that METTL7B is closely related to lipid metabolism and atherosclerosis. And further analysis also indicated that METTL7B could regulate 104 kinds of lipids, such as Lipid-n-0041, Lipid-n-0056, Lipid-n-0057, Lipid-n-0098, Lipid-n-0099 and Lipid-n-0169, mediated by AKR1C1, CETP and RORA. This study reveals a new mechanism for the occurrence and development of AS, thereby providing a potential target for the treatment of AS.

In conclusion, METTL7B can be used as a predictor and therapeutic target for AS.

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甲基转移酶METTL7B与动脉粥样硬化的相关性

动脉粥样硬化（AS）是严重威胁人类健康的疾病。虽然葡萄糖平衡、脂质代谢、炎症和高血压与AS密切相关，但甲基转移酶样（methyltransferase-like， METTL）家族成员是否参与AS的发生发展尚不清楚。分析GSE43292和GSE100927数据库中AS和正常血管中METTLs的差异表达基因。采用随机森林筛选筛选标记基因，选择两个数据库中的交叉基因。采用GSE28829/GSE41571和临床组织样本进行验证。利用这些数据库进一步分析标记基因的组织和细胞定位及其与脂质代谢和efferocytosis的相关性。从GSE43292和GSE100927数据库中分别获得7个和17个METTL差异表达基因。证实METTL7B和METTL5为交叉标记基因。与对照组相比，METTL7B在晚期AS、AS破裂斑块和临床重负荷斑块组织中的表达显著升高。ROC曲线分析显示，METTL7B在GSE28829和GSE41571中的AUC均大于0.9。此外，我们发现METTL7B与脂质代谢相关基因显著相关，促进脂滴形成。METTL7B与动脉粥样硬化和巨噬细胞介导的efferocytosis呈正相关。RNA-seq和靶向脂质组学结果也证实了METTL7B与脂质代谢和动脉粥样硬化密切相关。进一步分析还发现，METTL7B可以调节由AKR1C1、CETP和RORA介导的脂质，包括Lipid-n-0041、Lipid-n-0056、Lipid-n-0057、Lipid-n-0098、Lipid-n-0099和Lipid-n-0169等104种脂质。本研究揭示了AS发生发展的新机制，从而为AS的治疗提供了潜在靶点。综上所述，METTL7B可作为as的预测因子和治疗靶点。

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.