Fig. 6

CAB39L exerted an anti-Warburg effect in gastric cancer cells. a RNA-seq analysis and Gene Set Enrichment Analysis (GSEA) analysis demonstrated that the transcriptome profile of AGS-CAB39L cells was positively enriched for oxidative phosphorylation compared to control AGS cells; while CAB39L silencing in MKN74 cells was negatively correlated with oxidative phosphorylation. b Top three KEGG pathways associated with CAB39L in gastric cancer cell lines. c Overexpression of CAB39L induced PGC1α phosphorylation, whilst CAB39L knockdown produced an opposite effect. d CAB39L positively regulated the expression of multiple enzymes involved in oxidative phosphorylation, as evidenced by gain-of-function and loss-of-function experiments. e Non-targeted metabolomics profiling of AGS cells stably expressing empty vector or CAB39L. Ortho-partial least square-discriminant analysis (OPLS-DA) of the metabolite profile showed a clear separation of AGS-control and AGS-CAB39L. f Effect of ectopic CAB39L expression on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). AGS and BGC823 cells with over-expression of CAB39L showed significant increase in basal OCR, maximal OCR and the OCR-to-ECAR ratio and decreased lactate production rate. g In MKN74 cells, knockdown of CAB39L decreased ATP production, basal/maximal respiration, OCR-to-EACR ratio and increased lactate production rate. (*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.001)