FGF21 affects the glycolysis process via mTOR-HIF1α axis in hepatocellular carcinoma.

Abstract

Background: Metabolic reprogramming, particularly glycolysis, is essential in processes like cancer and immune response. While FGF21's role in hepatocyte glucose metabolism has been linked to glucose transporters and its impact on aerobic glycolysis and cellular growth in HCC remain unclear. In this study, we investigated FGF21-mediated modulation of glucose metabolism in HCC through mTOR and HIF1α axis in HCC.

Methods: The study evaluated the dysregulation of FGF21 and its prognostic impact in HCC using various datasets. The literature review was done to identify glycolysis related genes to find significant interaction with FGF21 using stringdb and their correlation in datasets. The regulation of FGF21 was validated in HepG2 cell lines by transfecting FGF21 and measuring its effects on glycolysis, including glucose uptake, lactate levels, and key glycolytic enzymes using rt-PCR. Additionally, the effect of FGF21 transfection on mTOR and HIF1α was also evaluated using rt-PCR.

Results: The insilico analysis indicates that the FGF21-mTOR-HIF1α signaling axis regulates glucose metabolism, with mTOR as a central integrator of signals from FGF21 and HIF1α. Invitro experiments showed that silencing FGF21 expression via siRNA reduced glycolytic enzyme expression, glucose uptake, lactate levels, and cell proliferation in HepG2 cells. Conversely, recombinant FGF21 treatment has a reverse effect in HepG2 cells. Additionally, FGF21 treatment also affected mTOR and HIF1α expression, highlighting its role in metabolic regulation and disease through the mTOR-HIF1α axis.

Conclusion: The regulation of FGF21 influences glycolysis via the mTOR-HIF1α axis, highlighting its critical role in glucose metabolism and metabolic adaptation in response to energy availability.