Fig. 1: LDHB silencing impairs GSH metabolism in KRAS-dependent NSCLC cells.
From: Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer
a Metabolomic analysis (LC-MS) of LDHB KD (siLDHB) and control (siNT) A549 cells (48 h post-transfection). Heat map showing the top 30 metabolites significantly different between LDHB KD and control A549 cells (n = 12). Relative abundance is scaled between 2 to -2. b Pathway enrichment analysis shows significantly downregulated metabolic processes in LDHB KD compared to control A549 cells. c Schematic of de novo GSH synthesis and the effect of LDHB KD on the pathway. Highlighted in blue are the genes and metabolites significantly altered by LDHB KD in A549 cells. Cys, cysteine; Cysta, cystathionine; γ-GC, γ-glutamylcysteine; Gly, glycine; Gln, glutamine; Glu, glutamate; GSH, glutathione; GSSG, glutathione disulfide; GCLC/GCLM, glutamate-cysteine ligase (GCL) catalytic and modifier subunits; GSS, glutamine synthetase; GSR, glutathione reductase; xCT, SLC7A11. d Heat map illustrating the abundance of key GSH metabolites in LDHB KD and control A549 cells. e The abundance of GSH, GSSG, and GSH/GSSG ratio in LDHB KD and control A549 cells. The analysis was based on the LC-MS data of A549 cells, p values by Student’s t-test. f LDHB KD downregulates GSH metabolism gene signature. GSEA was based on the transcriptome of LDHB KD (siLDHB) and control (siNT) A549 cells. g Ratios of GSH/GSSG in LDHB KD and control cells transfected with siRNAs for 48 h. Data are shown as mean ± s.d. (n = 3), with p values by Student’s t-test.
