Ma Jianguo, Xu Rongyi, Li Renlin, Fu Yangyang, Xu Jing, Zhou Lei, Qi Yan
The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China.
College of Acupuncture and Massage, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China.
PLoS One. 2025 May 28;20(5):e0321757. doi: 10.1371/journal.pone.0321757. eCollection 2025.
Non-alcoholic fatty liver disease (NAFLD) is prevalent worldwide and seriously affects health. M6A methylation is crucial in its pathogenesis. In this study, a thorough analysis of three gene expression datasets identified nine key differentially expressed genes DEGs associated with m6A methylation in NAFLD that are involved in important biological processes. Subsequently, functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), gene set variation analysis (GSVA) and immune infiltration analysis were conducted to explore the molecular mechanism and gene expression patterns. The LASSO risk model contains a total of 5 m6A-related differentially expressed genes (m6A-RDEGs)(RBM15, IGF2BP2, EIF3B, YTHDC1, WTAP), and the diagnostic model based on these key genes has high accuracy. Among them, YTHDC1 and WTAP are used as prominent biomarkers. In addition, an interaction network between mRNA and miRNA, RNA-binding protein (RBP), transcription factor (TF) and drugs is also constructed. Finally, the animal model of NAFLD was successfully established and validated by RT-qPCR and western blot. This study provides a valuable tool for clinical diagnosis and drives the progress of NAFLD research.
非酒精性脂肪性肝病（NAFLD）在全球范围内普遍存在，严重影响健康。m6A甲基化在其发病机制中至关重要。在本研究中，对三个基因表达数据集进行了全面分析，确定了九个与NAFLD中m6A甲基化相关的关键差异表达基因（DEGs），这些基因参与重要的生物学过程。随后，进行了功能富集分析、加权基因共表达网络分析（WGCNA）、基因集变异分析（GSVA）和免疫浸润分析，以探索分子机制和基因表达模式。LASSO风险模型共包含5个与m6A相关的差异表达基因（m6A-RDEGs）（RBM15、IGF2BP2、EIF3B、YTHDC1、WTAP），基于这些关键基因的诊断模型具有较高的准确性。其中，YTHDC1和WTAP作为突出的生物标志物。此外，还构建了mRNA与miRNA、RNA结合蛋白（RBP）、转录因子（TF）和药物之间的相互作用网络。最后，通过RT-qPCR和western blot成功建立并验证了NAFLD动物模型。本研究为临床诊断提供了有价值的工具，并推动了NAFLD研究的进展。
