METTL3 Represses FDX1 Expression Through m6A Methylation to Facilitate the Malignant Progression of Breast Cancer.
N6-methyladenosine (m6A) RNA methylation, dynamically regulated by methyltransferases, determines RNA fate and impacts tumorigenesis, yet the linkage between FDX1 gene expression and m6A modification in breast cancer (BC) remains unclear. Through bioinformatics analysis of The Cancer Genome Atlas (TCGA) database and experimental validation by qRT-PCR, we found that FDX1 is downregulated in BC tissues and cells. Functional assays including colony formation, Transwell, and apoptosis detection demonstrated that FDX1 upregulation inhibited proliferation, migration, invasion, and promoted apoptosis. Mechanistically, the m6A methyltransferase METTL3 was highly expressed in BC and suppressed FDX1 expression via m6A methylation, as confirmed by MeRIP-qPCR and RNA stability analysis. This METTL3-mediated m6A modification of FDX1 accelerated BC malignant progression. Our study elucidates that the METTL3-FDX1 axis plays an instrumental role in BC progression, revealing a novel epigenetic regulatory mechanism.