Panoply™ Human EGR1 Over-expressing Stable Cell Line

Hepatocellular carcinoma (HCC) is a major global public health challenge; however, current therapeutic outcomes remain suboptimal, and available therapeutic targets are limited. In this study, researchers identified early growth response factor 1 (EGR1) as a transcriptional target in HCC, investigated its function, and evaluated the potential of EGR1-based gene therapy for treating the disease. The results demonstrated that EGR1 expression was significantly reduced in HCC tissues. Downregulation of EGR1 promoted HCC cell proliferation and xenograft tumor growth, whereas EGR1 overexpression inhibited these processes. Furthermore, the efficacy of EGR1 gene therapy was validated using in vivo mouse HCC models and in vitro human liver cancer organoid models, confirming the anti-cancer role of EGR1 in HCC. Mechanistic analysis revealed that EGR1 interacts with the promoter region of liver-type phosphofructokinase-1 (PFKL), thereby suppressing PFKL gene expression and blocking PFKL-mediated aerobic glycolysis. Additionally, the study found that EGR1 enhances the sensitivity of HCC cells and xenograft tumors to sorafenib.

To elucidate the molecular mechanisms by which EGR1 inhibits hepatocellular carcinoma (HCC) growth, researchers performed RNA-seq analysis on EGR1-overexpressing PLC/PRF5 cells. Gene Set Enrichment Analysis (GSEA) revealed that EGR1 significantly downregulated the glycolysis pathway (Figure 1A). Aerobic glycolysis (the Warburg effect) is recognized as a hallmark of cancer and plays a crucial role in disease progression. Subsequently, RNA-seq analysis was performed on MHCC97H cells with EGR1 knockdown; GSEA showed that the loss of EGR1 led to the upregulation of the glycolysis pathway (Figure 1B). Glycolysis serves as a primary source of ATP for many tumor cells. To validate the impact of EGR1 on glycolysis in HCC cells, the researchers measured glucose uptake and lactate levels in EGR1-overexpressing PLC/PRF5 cells and EGR1-knockdown MHCC97H cells. The results demonstrated that EGR1 overexpression reduced glucose uptake and extracellular lactate levels in PLC/PRF5 cells, whereas EGR1 knockdown increased these parameters in MHCC97H cells (Figures 1C, D). Furthermore, extracellular acidification rate (ECAR) assays showed that EGR1 overexpression significantly reduced glycolytic rate and glycolytic capacity, while EGR1 knockdown increased them (Figure 1E). Measurements of ATP levels revealed that EGR1 overexpression reduced ATP levels in HCC cells, whereas EGR1 knockdown increased them (Figure 1F). These results confirm that EGR1 inhibits aerobic glycolysis in HCC.

Figure 1. EGR1 suppressed aerobic glycolysis in HCC cells. (Pan M, et al., 2024)