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S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells
Wang, Yan1,2; Sun, ZhongSheng3; Szyf, Moshe2; Moshe Szyf
2017-12-19
发表期刊ONCOTARGET
通讯作者邮箱moshe.szyf@mcgill.ca
ISSN1949-2553
文章类型Article
卷号8期号:67页码:111866-111881
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摘要

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo-protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent.

关键词epigenetic S-adenosyl methionine liver cancer mRNA sequencing capture bisulfite sequencing
DOI10.18632/oncotarget.22942
收录类别SCI
语种英语
项目资助者China-Canada team grant from the Canadian Institute of Health Research ; National Science Fund of China
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
WOS记录号WOS:000419567000090
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]HUMAN HEPATOCELLULAR-CARCINOMA ; CHOLINE-DEVOID DIET ; ACID-DEFINED DIETS ; BREAST-CANCER ; EXPRESSION ANALYSIS ; DNA METHYLATION ; BINDING PROTEIN ; RAS ONCOGENES ; GENOME-WIDE ; IN-VITRO
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/26031
专题中国科学院心理健康重点实验室
通讯作者Moshe Szyf
作者单位1.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
2.McGill Univ Montreal, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
3.Chinese Acad Sci, Beijing Inst Life Sci, Beijing, Peoples R China
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Wang, Yan,Sun, ZhongSheng,Szyf, Moshe,et al. S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells[J]. ONCOTARGET,2017,8(67):111866-111881.
APA Wang, Yan,Sun, ZhongSheng,Szyf, Moshe,&Moshe Szyf.(2017).S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.ONCOTARGET,8(67),111866-111881.
MLA Wang, Yan,et al."S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells".ONCOTARGET 8.67(2017):111866-111881.
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