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Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism

文献类型：期刊论文

作者Cai, Ling-Yan1; Chen, Shi-Jie2; Xiao, Sen-Hao2,3; Sun, Qin-Juan1; Ding, Chen-Hong4; Zheng, Bai-Nan4; Zhu, Xin-Yan1; Liu, Shu-Qing4; Yang, Feng2; Yang, Ya-Xi2
刊名CANCER RESEARCH
出版日期2021-02-15
卷号81期号:4页码:860-872
ISSN号0008-5472
DOI10.1158/0008-5472.CAN-20-1323
文献子类Article
英文摘要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, AT1C, and UTYMK. 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. Significance: 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.
WOS关键词HISTONE ; EXPRESSION
WOS研究方向Oncology
语种英语
WOS记录号WOS:000620166400011
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/309395]  
专题新药研究国家重点实验室
通讯作者Zhang, Xin; Xie, Wei-Fen
作者单位1.Tongji Univ, Dept Gastroenterol, Sch Med, Shanghai East Hosp, Shanghai, Peoples R China;
2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Mod, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China;
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China;
4.Second Mil Med Univ, Changzheng Hosp, Dept Gastroenterol, Shanghai 200003, Peoples R China;
5.Pilot Natl Lab Marine Sci & Technol, Open Studio Druggabil Res Marine Nat Prod, Qingdao, Peoples R China
推荐引用方式
GB/T 7714		 Cai, Ling-Yan,Chen, Shi-Jie,Xiao, Sen-Hao,et al. Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism[J]. CANCER RESEARCH,2021,81(4):860-872.
APA Cai, Ling-Yan.,Chen, Shi-Jie.,Xiao, Sen-Hao.,Sun, Qin-Juan.,Ding, Chen-Hong.,...&Xie, Wei-Fen.(2021).Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism.CANCER RESEARCH,81(4),860-872.
MLA Cai, Ling-Yan,et al."Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism".CANCER RESEARCH 81.4(2021):860-872.

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来源：上海药物研究所

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