Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma
	Liu, Jiao ; Jiang, Jinhua ; Mo, Jiezhen ; Liu, Dan ; Cao, Dan ; Wang, Hailin ; He, Yufei ; Wang, Hongyang
刊名	HEPATOLOGY
	2019
卷号	69 期号:1 页码:196-208
ISSN号	0270-9139
英文摘要	Methylation of the fifth position of cytosine (5mC) is an important epigenetic modification of DNA. It has been shown that the oxidized derivatives of 5mC, namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), are in dynamic existence and have distinct regulatory functions. In the current study, we investigated whether there are changes in the contents of all three 5mC-oxidized derivatives in the hepatocellular carcinoma (HCC) genome and further explored the underlying mechanisms. We showed that both global genomic 5hmC and 5fC contents were decreased significantly in the very early stage (stage 0, Barcelona Clinic Liver Cancer [BCLC] staging) of HCC compared with those of paratumor tissues. Noteworthily, 5fC content continued to decrease in the late stage (BCLC staging from 0 to A) of HCC. The 5caC content in HCC tissues was below the detection threshold. Hepatitis B virus (HBV) infection was associated with 5mC, 5hmC, or 5fC decrease in HCC; and measurements in cell lines integrated with or without HBV DNA showed consistent results. On the other hand, both the expression level of ten-eleven translocation enzyme 2 (TET2) and alpha-ketoglutarate content were decreased significantly in HCC. The significantly positive correlations among the expression levels of DNA methylation-related enzymes in paratumor tissues were generally attenuated or even disappeared in HCC tumor tissues. The decreases of both 5hmC and 5fC contents in genomic DNA were associated with poor prognosis of HCC patients. Conclusion: Global 5hmC and 5fC contents were decreased significantly in the very early stage of HCC; the decrease of 5hmC and 5fC was mainly due to the decrease of 5mC and associated with HBV infection, decreased TET enzyme activity, and uncoordinated expression of DNA methylation-related enzymes.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/42952]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
作者单位	1.Eastern Hepatobiliary Surg Hosp, Natl Ctr Liver Canc, 225 Changhai Rd, Shanghai 200438, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Renji Hosp,Sch Med, Shanghai, Peoples R China 3.Eastern Hepatobiliary Surg Inst Hosp, Int Cooperat Lab Signal Transduct, 225 Changhai Rd, Shanghai 200438, Peoples R China 4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Shuangqing Rd 18, Beijing 100085, Peoples R China 5.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Liu, Jiao,Jiang, Jinhua,Mo, Jiezhen,et al. Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma[J]. HEPATOLOGY,2019,69(1):196-208.
APA	Liu, Jiao.,Jiang, Jinhua.,Mo, Jiezhen.,Liu, Dan.,Cao, Dan.,...&Wang, Hongyang.(2019).Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma.HEPATOLOGY,69(1),196-208.
MLA	Liu, Jiao,et al."Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma".HEPATOLOGY 69.1(2019):196-208.