Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model

Abstract It is an important cause of death in old age to rupture an abdominal aortic aneurysm. The pathogenesis of AAA has not been fully elucidated, and m6A RNA methylation regulators have never been implicated in AAA development. This study aimed to explore the expression profile, potential functi...

Full description

Saved in:
Bibliographic Details
Main Authors: Julin Wang, Tianyu Miao, Yanyun Wang, Tiehao Wang, Zhangyu He, Fei Xiong, Ding Yuan, Qiang Guo, Yi Yang, Zhichen Tang, Bin Huang, Jichun Zhao
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-03760-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849688404149665792
author Julin Wang
Tianyu Miao
Yanyun Wang
Tiehao Wang
Zhangyu He
Fei Xiong
Ding Yuan
Qiang Guo
Yi Yang
Zhichen Tang
Bin Huang
Jichun Zhao
author_facet Julin Wang
Tianyu Miao
Yanyun Wang
Tiehao Wang
Zhangyu He
Fei Xiong
Ding Yuan
Qiang Guo
Yi Yang
Zhichen Tang
Bin Huang
Jichun Zhao
author_sort Julin Wang
collection DOAJ
description Abstract It is an important cause of death in old age to rupture an abdominal aortic aneurysm. The pathogenesis of AAA has not been fully elucidated, and m6A RNA methylation regulators have never been implicated in AAA development. This study aimed to explore the expression profile, potential functions and regulated mechanism of m6A RNA methylation in the abdominal aortic aneurysm mice model. A successful AAA mouse model was established using Ang II. M6A- methylated RNA Immunoprecipitation (MeRIP) sequencing and RNA sequencing were performed to identify the m6A sites in the abdominal aorta walls samples. The expression of m6A methylation regulators was analyzed in the datasets and MeRIP-qPCR was performed to verify the results of MeRIP-sequencing. Bioinformatics analysis was used to evaluate the m6A patterns and indicate the potential signaling pathway. There were 2039 differentially methylated m6A peaks involving 1865 mRNAs in the AAA group relative to the control, of which 1610 peaks in 1466 mRNAs were hypermethylated, and 429 peaks in 410 mRNAs were hypomethylated. The hypermethylated mRNAs in AAA group were primarily enriched in transcription regulation and intercellular signaling, especially the Wnt signaling-associated processes. Hypomethylated m6A sites were mainly enriched in G protein-coupled receptor activity and ion channel activity. MeRIP-qPCR suggested that the sequencing data were reliable and accurate. The mRNA expression of 24 m6A regulators showed no obvious difference between AAA and the control group, but the m6A methylation levels of three components of methyltransferases complex and one ‘readers’ were significantly increased. Our study suggested an original viewpoint that the m6A modification might be regulated by several unidentified regulation modes or genes in the Ang II-induced AAA mice model, and be closely relevant to the combined effect of m6A methylation modification in the Wnt pathway, G protein-coupled receptor, and ion channel-associated genes, which were worthy of further investigation.
format Article
id doaj-art-e31d998d3143405299cd81c38aac1795
institution DOAJ
issn 2045-2322
language English
publishDate 2025-05-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-e31d998d3143405299cd81c38aac17952025-08-20T03:22:02ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-03760-8Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse modelJulin Wang0Tianyu Miao1Yanyun Wang2Tiehao Wang3Zhangyu He4Fei Xiong5Ding Yuan6Qiang Guo7Yi Yang8Zhichen Tang9Bin Huang10Jichun Zhao11Department of Vascular Surgery, West China Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityWest China School of Basic Sciences and Forensic Medicine, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityDepartment of Vascular Surgery, West China Hospital, Sichuan UniversityAbstract It is an important cause of death in old age to rupture an abdominal aortic aneurysm. The pathogenesis of AAA has not been fully elucidated, and m6A RNA methylation regulators have never been implicated in AAA development. This study aimed to explore the expression profile, potential functions and regulated mechanism of m6A RNA methylation in the abdominal aortic aneurysm mice model. A successful AAA mouse model was established using Ang II. M6A- methylated RNA Immunoprecipitation (MeRIP) sequencing and RNA sequencing were performed to identify the m6A sites in the abdominal aorta walls samples. The expression of m6A methylation regulators was analyzed in the datasets and MeRIP-qPCR was performed to verify the results of MeRIP-sequencing. Bioinformatics analysis was used to evaluate the m6A patterns and indicate the potential signaling pathway. There were 2039 differentially methylated m6A peaks involving 1865 mRNAs in the AAA group relative to the control, of which 1610 peaks in 1466 mRNAs were hypermethylated, and 429 peaks in 410 mRNAs were hypomethylated. The hypermethylated mRNAs in AAA group were primarily enriched in transcription regulation and intercellular signaling, especially the Wnt signaling-associated processes. Hypomethylated m6A sites were mainly enriched in G protein-coupled receptor activity and ion channel activity. MeRIP-qPCR suggested that the sequencing data were reliable and accurate. The mRNA expression of 24 m6A regulators showed no obvious difference between AAA and the control group, but the m6A methylation levels of three components of methyltransferases complex and one ‘readers’ were significantly increased. Our study suggested an original viewpoint that the m6A modification might be regulated by several unidentified regulation modes or genes in the Ang II-induced AAA mice model, and be closely relevant to the combined effect of m6A methylation modification in the Wnt pathway, G protein-coupled receptor, and ion channel-associated genes, which were worthy of further investigation.https://doi.org/10.1038/s41598-025-03760-8Abdominal aortic aneurysmm6AMethylationMice modelWnt pathwaymRNA
spellingShingle Julin Wang
Tianyu Miao
Yanyun Wang
Tiehao Wang
Zhangyu He
Fei Xiong
Ding Yuan
Qiang Guo
Yi Yang
Zhichen Tang
Bin Huang
Jichun Zhao
Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
Scientific Reports
Abdominal aortic aneurysm
m6A
Methylation
Mice model
Wnt pathway
mRNA
title Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
title_full Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
title_fullStr Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
title_full_unstemmed Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
title_short Altered expression and potential role of N6-methyladenosine mRNA methylation in abdominal aortic aneurysm mouse model
title_sort altered expression and potential role of n6 methyladenosine mrna methylation in abdominal aortic aneurysm mouse model
topic Abdominal aortic aneurysm
m6A
Methylation
Mice model
Wnt pathway
mRNA
url https://doi.org/10.1038/s41598-025-03760-8
work_keys_str_mv AT julinwang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT tianyumiao alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT yanyunwang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT tiehaowang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT zhangyuhe alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT feixiong alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT dingyuan alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT qiangguo alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT yiyang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT zhichentang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT binhuang alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel
AT jichunzhao alteredexpressionandpotentialroleofn6methyladenosinemrnamethylationinabdominalaorticaneurysmmousemodel