M6A methyltransferase METTL3 promotes glucose metabolism hub gene expression and induces metabolic dysfunction-associated steatotic liver disease (MASLD)

作者：Shuowen Wang, Ziying Xu, Z.L. Wang, Xiaoyu Yi, Jianxin Wu · 发表于：BMC Genomics · 年份：2025 · DOI：10.1186/s12864-025-11377-4 · 被引用次数：6 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Metalloenzymes and iron-sulfur proteins

BACKGROUND: N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of METTL3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. METHODS: An MASLD mouse model was established by feeding C57BL/6J mice a high-fat diet for 12 weeks. A METTL3 stable overexpression AML12 cell model was also constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. RESULTS: METTL3 expression was significantly increased in the MASLD mouse model. Through our transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between the transcriptomic and proteomic datasets. GO/ KEGG enrichment analyses identified terms that may be involved in post-transcriptional modifications, particularly METTL3-mediated m6A modification. Subsequently, through integrated proteomic analysis of the METTL3-overexpressed AML12 cell model and the MASLD mouse model, we selected the top 20 co-upregulated and co-downregulated GO/ KEGG terms as the main biological processes influenced by METTL3 during MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/ KEGG terms affected by METTL3-induced m6A modification. Prote...