Fig 1: MAT2A contributes to cell proliferation via fatty acid biosynthesis(A) Heatmap of significant proteins in gene sets of fatty acid biosynthesis and biosynthesis of unsaturated fatty acids from KEGG in proteomics data of H1299 with siMAT2A-1 or 5 μM AG-270; proteins with p < 0.05 (two-tailed Student’s t test), and FC < 0.83 or FC > 1.2 are considered significant.(B) GSEA analysis of fatty acid metabolism in proteomics data of H1299 with siMAT2A-1 or 5 μM AG-270.(C) Western blot analysis of FASN and SCD in H1299 with siMAT2A-1 or 5 μM AG-270. β-Actin was used as a loading control.(D) Untargeted metabolomics analysis of palmitic acid (PA) and oleic acid (OA) levels in H1299 with siMAT2A-1 (n = 6).(E) qPCR analysis of FASN and SCD in H1299 with siMAT2A-1 or 5 μM AG-270 (n = 3).(F and G) ATAC-seq analysis of FASN (F) and SCD (G) in H1299 with siMAT2A-1 (n = 2). Plots were generated using IGV software (version 2.19.2).(H and I) Relative cell viability in H1299 treated with different concentrations of AG-270 and 2.5 μM PA (H), and representative combination result of 5 μM AG-270 and 2.5 μM PA (I) (n = 3).(J) The crystal violet staining result of H1299 treated with 1.5 μM AG-270 and 2.5 μM PA (n = 3).(K) Combination results of H1299 treated with AG-270 and TVB-2640, showing HSA score = 22.93, indicating strong synergetic effect (n = 3).Data are presented as mean ± SD (E–K); statistical significance was determined by two-tailed Student’s t test (D–G) or one-way ANOVA (I-K) or two-way ANOVA (H), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001. SynergyFinder plus was used for drug combination results analysis (K). Experiments were repeated three times independently (C, E, H-K). See also Figure S3.