S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

Yan Wang; ZhongSheng Sun; Moshe Szyf

doi:10.18632/oncotarget.22942

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Research Papers:

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

Yan Wang, ZhongSheng Sun and Moshe Szyf _

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Oncotarget. 2017; 8:111866-111881. https://doi.org/10.18632/oncotarget.22942

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Abstract

Yan Wang1,2, ZhongSheng Sun3 and Moshe Szyf2

1CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China

2Department of Pharmacology and Therapeutics, McGill University Montreal, Quebec, Canada

3Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China

Correspondence to:

Moshe Szyf, email: [email protected]

Keywords: epigenetic; S-adenosyl methionine; liver cancer; mRNA sequencing; capture bisulfite sequencing

Received: January 23, 2017 Accepted: July 29, 2017 Published: December 05, 2017

ABSTRACT

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.

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Research Papers:

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

Abstract