Hypoxia-inducible factor 1-alpha and lactate dehydrogenase-A axis in metabolic changes and aggression in esophageal squamous-cell carcinoma

Figure 4 Hypoxia-inducible factor 1-alpha-mediated regulation of lactate dehydrogenase A expression in esophageal squamous-cell carcinoma. A: Representation predicted binding motif of hypoxia-inducible factor 1-alpha (HIF1A); B: Venn diagram showing overlap between differentially expressed genes (DEGs) in esophageal squamous-cell carcinoma (ESCC) and genes identified in the ChIP-seq database for HIF1A binding sites. A total of 12 common genes are highlighted; C: Interaction network of HIF1A with common DEGs and key metabolic enzymes in ESCC; D: Relative mRNA levels of lactate dehydrogenase A (LDHA) in 21 paired ESCC patient tissues; E: LDHA mRNA levels decrease significantly upon HIF1A knockdown in ESCC cells; F: Luciferase assay demonstrating the transcriptional activity of LDHA promoter; G: Analysis of LDHA promoter mutations affecting HIF1A binding. ESCC: Esophageal squamous-cell carcinoma; LDHA: Lactate dehydrogenase A; HIF1A: Hypoxia-inducible factor 1-alpha; siNTC: Non-targeting control siRNA; siHIF1A: HIF1A-targeting siRNA.