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

• Published in: The FASEB journal 2024-01, Vol.38 (2), p.e23444-n/a
• Main Authors: He, Xian‐lu, Guo, Hui‐jie, Lei, Ya‐ruo, Li, Jun, Li, Jing‐yi, Li, Min‐hui, Li, Na, Wang, Fei, Mo, Chun‐fen
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; HCC; Hepatitis B virus; Humans; Lipogenesis; Liver Neoplasms - genetics; Liver Neoplasms - virology; NAMPT; Nicotinamide Phosphoribosyltransferase - genetics; SREBP1
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202300070RRR

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. NAMPT was upregulated in HBV‐positive HCC tissues and activated SREBP1 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, and ultimately the malignant progression in HBV‐associated HCC cells.