PMID- 21450690
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20110422
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 43
IP  - 5
DP  - 2011 May
TI  - Hepatitis C virus core upregulates the methylation status of the RASSF1A promoter 
      through regulation of SMYD3 in hilar cholangiocarcinoma cells.
PG  - 354-61
LID - 10.1093/abbs/gmr021 [doi]
AB  - 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.
FAU - Guo, Ning
AU  - Guo N
AD  - Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University, Guangzhou 510120, China.
FAU - Chen, Rufu
AU  - Chen R
FAU - Li, Zhihua
AU  - Li Z
FAU - Liu, Yonggang
AU  - Liu Y
FAU - Cheng, Di
AU  - Cheng D
FAU - Zhou, Quanbo
AU  - Zhou Q
FAU - Zhou, Jiajia
AU  - Zhou J
FAU - Lin, Qing
AU  - Lin Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110329
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (DNA Primers)
RN  - 0 (Hepatitis C Antigens)
RN  - 0 (RASSF1 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (SMYD3 protein, human)
SB  - IM
MH  - Base Sequence
MH  - Bile Duct Neoplasms/*genetics/pathology
MH  - Bile Ducts, Intrahepatic/*pathology
MH  - Blotting, Western
MH  - Cholangiocarcinoma/*genetics/pathology
MH  - DNA Methylation/*immunology
MH  - DNA Primers
MH  - Hepatitis C Antigens/*immunology
MH  - Histone-Lysine N-Methyltransferase/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/*genetics
MH  - *Up-Regulation
EDAT- 2011/04/01 06:00
MHDA- 2011/08/24 06:00
CRDT- 2011/04/01 06:00
PHST- 2011/04/01 06:00 [entrez]
PHST- 2011/04/01 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
AID - gmr021 [pii]
AID - 10.1093/abbs/gmr021 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2011 May;43(5):354-61. doi: 
      10.1093/abbs/gmr021. Epub 2011 Mar 29.