Preliminary study on circRNA N6-methyladenosine(m6A)methylation in hippocampus of APP / PS1 double transgenic mice with Alzheimer 's disease
10.3760/cma.j.issn.0254-9026.2025.02.013
- VernacularTitle:APP/PS1双转基因阿尔茨海默病小鼠海马组织环状RNA N6-甲基腺苷甲基化修饰的初步研究
- Author:
Linna YAN
1
;
Jing XIONG
1
;
Wenjing LYV
1
;
Xin ZHANG
1
;
Zixuan WANG
1
Author Information
1. 青岛大学附属医院老年医学科，青岛 266000
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
m6A methylation;
Circular RNA
- From:
Chinese Journal of Geriatrics
2025;44(2):188-193
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To assess the levels of circRNA and N6-methyladenosine(m6A)methylation in hippocampal tissue of Alzheimer's disease(AD)mice and wild-type(WT)mice, and to explore the potential role of circRNA m6A methylation modification in the pathogenesis of Alzheimer's disease.Methods:Differentially expressed circular RNAs(circRNAs)in the hippocampal tissue of APPswe/PS1dE9(APP/PS1)double-transgenic Alzheimer's disease(AD)model mice and matched wild type mice were identified using RNA high-throughput sequencing(RNA-seq).Subsequently, Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the source genes of these circRNAs.Validation of the RNA-seq results was performed using real-time quantitative PCR(qRT-PCR).Furthermore, the SRAMP website was utilized to predict potential m6A modification sites on the differentially expressed circRNAs.Finally, circRNAs with high confidence were validated and analyzed through methylated RNA immunoprecipitation-quantitative PCR(MeRIP-qPCR).Results:In comparison to the control group, 21 circRNAs exhibited differential expression in the APP/PS1 group, with 15 being up-regulated and 6 down-regulated.GO analysis revealed that the source genes of these differentially expressed circRNAs were primarily associated with synapse structure and function, while KEGG analysis indicated their involvement in the Hippo signaling pathway and Lipid metabolism.qRT-PCR results confirmed that the expression patterns of the differentially expressed circRNAs were consistent with the RNA-seq findings.Specifically, the expression of mmu-Bai3_0007 in the APP/PS1 group was significantly lower than that in the control group(0.033±0.002 vs.1.006±0.136, t=12.38, P<0.01), and the m6A methylation level of mmu-Bai3_0007 was also notably reduced in the APP/PS1 group compared to the control group(0.144±0.018 vs.0.431±0.087, t=5.62, P<0.01). Conclusions:The m6A methylation modification of Bai3circRNA could play a role in Alzheimer's disease by regulating the expression of Bai3 circRNA.
