Wang Julin, Miao Tianyu, Wang Yanyun, Wang Tiehao, He Zhangyu, Xiong Fei, Yuan Ding, Guo Qiang, Yang Yi, Tang Zhichen, Huang Bin, Zhao Jichun
Department of Vascular Surgery, West China Hospital, Sichuan University, 37 GuoXue Alley, Chengdu, 610041, Sichuan, People's Republic of China.
Laboratory 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 University, Chengdu, 610041, Sichuan, People's Republic of China.
Sci Rep. 2025 May 29;15(1):18893. doi: 10.1038/s41598-025-03760-8.
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 mA RNA methylation regulators have never been implicated in AAA development. This study aimed to explore the expression profile, potential functions and regulated mechanism of mA RNA methylation in the abdominal aortic aneurysm mice model. A successful AAA mouse model was established using Ang II. MA- methylated RNA Immunoprecipitation (MeRIP) sequencing and RNA sequencing were performed to identify the mA sites in the abdominal aorta walls samples. The expression of mA 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 mA patterns and indicate the potential signaling pathway. There were 2039 differentially methylated mA 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 mA 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 mA 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 mA 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 mA methylation modification in the Wnt pathway, G protein-coupled receptor, and ion channel-associated genes, which were worthy of further investigation.
腹主动脉瘤破裂是老年人重要的死亡原因。腹主动脉瘤的发病机制尚未完全阐明，且mRNA甲基化调节因子从未被认为与腹主动脉瘤的发生有关。本研究旨在探讨mRNA甲基化在腹主动脉瘤小鼠模型中的表达谱、潜在功能及调控机制。使用血管紧张素II建立了成功的腹主动脉瘤小鼠模型。进行了m6A-甲基化RNA免疫沉淀（MeRIP）测序和RNA测序，以鉴定腹主动脉壁样本中的m6A位点。在数据集中分析了m6A甲基化调节因子的表达，并进行了MeRIP-qPCR以验证MeRIP测序的结果。采用生物信息学分析来评估m6A模式并指出潜在的信号通路。与对照组相比，腹主动脉瘤组有2039个差异甲基化的m6A峰，涉及1865个mRNA，其中1466个mRNA中的1610个峰发生高甲基化，410个mRNA中的429个峰发生低甲基化。腹主动脉瘤组中高甲基化的mRNA主要富集在转录调控和细胞间信号传导，尤其是与Wnt信号相关的过程。低甲基化的m6A位点主要富集在G蛋白偶联受体活性和离子通道活性。MeRIP-qPCR表明测序数据可靠且准确。24个m6A调节因子的mRNA表达在腹主动脉瘤组和对照组之间无明显差异，但甲基转移酶复合物的三个组分和一个“读取器”的m6A甲基化水平显著升高。我们的研究提出了一个新观点，即在血管紧张素II诱导的腹主动脉瘤小鼠模型中，m6A修饰可能受几种未知的调控模式或基因调控，并且与Wnt途径、G蛋白偶联受体和离子通道相关基因中的m6A甲基化修饰的联合作用密切相关，值得进一步研究。
