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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-22
pubmed:abstractText
Increasing evidence has been accumulated indicating the important role of epigenetic regulation in tumor genesis. Previously, we observed that the transfection of hepatitis C virus core (HCVc) protein led to malignant transformation in normal biliary cells, and that tumor suppressor gene RASSF1A was downregulated in many hilar cholangiocarcinoma patients by hypermethylation in the promoter region. In the present study, we found SET and MYND domain-containing protein 3 (SMYD3), a novel histone methyltransferase, was overexpressed in cholangiocarcinoma patients especially in those with HCV infection. Transfection of HCVc into hilar cholangiocarcinoma cell lines QBC939 and FRH0201 could upregulate the expression of SMYD3 and promote cell growth, which was consistent with the results of our clinical research. This phenomenon indicated that SMYD3 was related to the epigenetic regulation of cholangiocarcinoma genesis with HCV infection. Overexpression of SMYD3 could inhibit RASSF1A expression, whereas inhibition of SMYD3 by siRNA improved its expression. Methylation-specific polymerase chain reaction (MS-PCR) results showed the methylation status of RASSF1A promoter was regulated by SMYD3. In conclusion, HCVc could upregulate the methylation status of the RASSF1A promoter through regulation of SMYD3, and histone methylation may affect the DNA methylation of downstream gene by an unknown mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1745-7270
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
354-61
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Hepatitis C virus core upregulates the methylation status of the RASSF1A promoter through regulation of SMYD3 in hilar cholangiocarcinoma cells.
pubmed:affiliation
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't