NAMPT promotes the malignant progression of HBV-associated hepatocellular carcinoma through activation of SREBP1-mediated lipogenesis.

Abstract

Metabolic reprogramming is a hallmark of cancer. The nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway maintains sufficient cellular NAD levels and is required for tumorigenesis and development. However, the molecular mechanism by which NAMPT contributes to HBV-associated hepatocellular carcinoma (HCC) remains not fully understood. In the present study, our results showed that NAMPT protein was obviously upregulated in HBV-positive HCC tissues compared with HBV-negative HCC tissues. NAMPT was positively associated with aggressive HCC phenotypes and poor prognosis in HBV-positive HCC patients. NAMPT overexpression strengthened the proliferative, migratory, and invasive capacities of HBV-associated HCC cells, while NAMPT-insufficient HCC cells exhibited decreased growth and mobility. Mechanistically, we demonstrated that NAMPT activated SREBP1 (sterol regulatory element-binding protein 1) by increasing the expression and nuclear translocation of SREBP1, leading to the transcription of SREBP1 downstream lipogenesis-related genes and the production of intracellular lipids and cholesterol. Altogether, our data uncovered an important molecular mechanism by which NAMPT promoted HBV-induced HCC progression through the activation of SREBP1-triggered lipid metabolism reprogramming and suggested NAMPT as a promising prognostic biomarker and therapeutic target for HBV-associated HCC patients.