Characteristics and effect of mRNA m6A methylation modification mode in patients with major depressive disorder
10.3760/cma.j.cn371468-20240827-00393
- VernacularTitle:重度抑郁障碍患者mRNA m6A甲基化修饰模式的特征及作用
- Author:
Yuanbo LI
1
;
Zhaonan YANG
;
Liang LIU
;
Yanjie YANG
;
Siyuan KE
;
Kexin QIAO
;
Xiuxian YANG
Author Information
1. 哈尔滨医科大学心理科学与健康管理中心，哈尔滨 150081
- Publication Type:Journal Article
- Keywords:
Major depressive disorder;
m6A methylation;
mRNA;
m6A modification expression profile
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2025;34(7):625-632
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the characteristics of m6A methylation modification patterns in mRNA of patients with major depressive disorder (MDD) and its effect in the pathogenesis of the disease.Methods:From March 2022 to May 2023, five untreated MDD patients were assigned to the MDD group, and five healthy individuals were enrolled as the healthy control group at the First Psychiatric Hospital of Harbin.Microarray analysis was performed to determine the m6A modification profiles and gene expression patterns of mRNA in MDD. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were conducted to elucidate the effect of m6A methylation in the development of depression. Finally, methylated RNA immunoprecipitation combined with quantitative PCR (MeRIP-qPCR) was used to validate the m6A methylation levels of key mRNAs (GRM4, CAMKK2). Data were analyzed using R software (version 4.2.0) with t-test and Fisher's exact test. Results:Significant differences in m6A-modified mRNAs were observed between MDD patients and healthy controls. A total of 513 mRNAs (180 hypermethylated and 333 hypomethylated) exhibited differential m6A modifications in MDD patients. GO and KEGG analysis revealed that hypermethylated mRNAs were primarily enriched in neuroactive ligand-receptor interactions, while hypomethylated mRNAs were associated with the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, a total of 350 differentially expressed mRNAs were identified (171 upregulated and 179 downregulated), enriched in the cyclic adenosine monophosphate (cAMP) and tumor necrosis factor (TNF) signaling pathways. MeRIP-qPCR results demonstrated that the m6A methylation level of GRM4 in MDD patients (25.40±2.38) was significantly higher than that in healthy controls (9.40±1.00) ( t=13.88, P<0.05), whereas the methylation level of CAMKK2 (19.63±6.60) was significantly lower than that in healthy controls (30.51±7.20) ( t=2.48, P<0.05). Conclusion:The m6A modification expression profile is abnormal in patients with major depressive disorder, which may be involved in the pathogenesis and development of MDD, and the identification of key pathways may provide new clues and evidence for the development of more effective therapeutic targets for MDD.
