Farnesyl Diphosphate Synthase Promotes Proliferation of Hepatocellular Carcinoma Cells by Interacting With...

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by metabolic reprogramming that supports tumour growth and survival. This study identifies farnesyl diphosphate synthase (FDPs), a key enzyme in the mevalonate pathway, as a critical regulator of HCC proliferation and apoptosis.

We applied bioinformatics analysis through TCGA and GSE database to identify the expression of FDPs within HCC patients. Then, mechanistic studies were conducted including Western blots, apoptosis assay, RT-qPCR, rescue assay, RNA-sequencing, in vivo study to prove the role of FDPs in regulating HCC progression.

FDPs was found to be significantly upregulated in HCC tissues, and its down-regulation promotes tumour cell apoptosis while inhibiting tumour cell proliferation in vitro and in vivo. Mechanistically, we identified FDPs regulate glucose-6-phosphate dehydrogenase (G6PD) by RNA sequencing, bioinformatics prediction, and rescue experiments, indicating its involvement in glycolysis regulation in tumour cells. The identification of this FDPs-G6PD axis suggests a novel metabolic pathway contributing to HCC development.

In summary, this study highlights FDPs play an essential oncogenic role in HCC, linking it to metabolic reprogramming and tumour survival. These findings establish FDPs as a promising therapeutic target, offering a foundation for further exploration of its regulatory mechanisms and potential clinical applications.