TFB2M activates aerobic glycolysis in hepatocellular carcinoma cells through the NAD+ /SIRT3/HIF-1α signaling.

Increased aerobic glycolysis has been well-known as a hallmark of cancer, which is closely related to mitochondrial dysfunction. TFB2M (mitochondrial transcription factor B2) is a core mitochondrial transcription factor, which has been shown by us to play an oncogenic role in hepatocellular carcinoma (HCC). However, whether TFB2M contributes to the aerobic glycolysis in HCC cells remains unexplored. The role and underlying molecular mechanisms of TFB2M in the regulation of aerobic glycolysis in HCC cells were systematically investigated by in vitro cell glucose metabolism and metabolomics analyses. Besides, the effects of TFB2M-regulated aerobic glycolysis in the growth and metastasis of HCC cells were also explored. Here, we show that TFB2M markedly enhanced the reprogramming of glucose metabolism from oxidative phosphorylation to aerobic glycolysis mainly through two mechanisms. On the one hand, TFB2M increased the expressions of glycolytic genes GAPDH, LDHA, GLUT1, and HK2. On the other hand, TFB2M decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a critical regulator of mitochondrial respiration. Mechanistically, TFB2M regulates the upregulation of glycolytic genes and downregulation of PGC-1α mainly through NAD+ /SIRT3/HIF-1α signaling. Additionally, we found that TFBM2 promoted the progression of HCC cells through HIF-1α-regulated reprogramming of glucose metabolism. Our findings indicate that TFB2M serves as a critical glucose metabolic reprogramming mechanism in tumorigenesis, which could be used as potential therapeutic target in HCC. © 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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Hulin Chang, Jibin Li, Ying Luo, Bing Wu, Chong Yuan, Xilin Geng. TFB2M activates aerobic glycolysis in hepatocellular carcinoma cells through the NAD+ /SIRT3/HIF-1α signaling. Journal of gastroenterology and hepatology. 2021 Oct;36(10):2978-2988

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PMID: 33982328

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