American Association for Cancer Research
00085472can201323-sup-241667_3_supp_6772398_ql0jj1.xls (330.5 kB)

Supplementary Table S7 from Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism

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posted on 2023-03-31, 04:06 authored by Ling-Yan Cai, Shi-Jie Chen, Sen-Hao Xiao, Qin-Juan Sun, Chen-Hong Ding, Bai-Nan Zheng, Xin-Yan Zhu, Shu-Qing Liu, Feng Yang, Ya-Xi Yang, Bing Zhou, Cheng Luo, Xin Zhang, Wei-Fen Xie

Supplementary Table S7. HPLC analysis of nucleotides


National Natural Science Foundation of China

Top-Level Clinical Discipline Project of Shanghai Pudong

Shanghai Sailing Program

Youth Innovation Promotion Association

Natural Science Foundation of Shanghai

Key New Drug Creation and Manufacturing Program



Targeting epigenetics in cancer has emerged as a promising anticancer strategy. p300/CBP is a central regulator of epigenetics and plays an important role in hepatocellular carcinoma (HCC) progression. Tumor-associated metabolic alterations contribute to the establishment and maintenance of the tumorigenic state. In this study, we used a novel p300 inhibitor, B029-2, to investigate the effect of targeting p300/CBP in HCC and tumor metabolism. p300/CBP–mediated acetylation of H3K18 and H3K27 increased in HCC tissues compared with surrounding noncancerous tissues. Conversely, treatment with B029-2 specifically decreased H3K18Ac and H3K27Ac and displayed significant antitumor effects in HCC cells in vitro and in vivo. Importantly, ATAC-seq and RNA-seq integrated analysis revealed that B029-2 disturbed metabolic reprogramming in HCC cells. Moreover, B029-2 decreased glycolytic function and nucleotide synthesis in Huh7 cells by reducing H3K18Ac and H3K27Ac levels at the promoter regions of amino acid metabolism and nucleotide synthesis enzyme genes, including PSPH, PSAT1, ALDH18A1, TALDO1, ATIC, and DTYMK. Overexpression of PSPH and DTYMK partially reversed the inhibitory effect of B029-2 on HCC cells. These findings suggested that p300/CBP epigenetically regulates the expression of glycolysis-related metabolic enzymes through modulation of histone acetylation in HCC and highlights the value of targeting the histone acetyltransferase activity of p300/CBP for HCC therapy. This study demonstrates p300/CBP as a critical epigenetic regulator of glycolysis-related metabolic enzymes in HCC and identifies the p300/CBP inhibitor B029-2 as a potential therapeutic strategy in this disease.