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Decreased PADI4 mRNA Association with Global Hypomethylation in Hepatocellular Carcinoma During HBV Exposure.
MedLine Citation:
PMID:  22907585     Owner:  NLM     Status:  Publisher    
To gain insight into the role of peptidylarginine deiminase type 4 (PADI4), we determined the relationship between PADI4 mRNA and global hypomethylation during HBV exposure in hepatocarcinogenesis. We analyzed Line-1 methylation by MSP, and CD133 mRNA by real-time PCR in 74 HCC. The HCC cancer lines (7721, Huh7, and Hep-G2) were treated with 5-Aza-CdR and TSA. PADI4 mRNA were lower in HCC tissues (Mean(-∆Ct) = 1.41) than that in Non-Hcc tissues (Mean(-∆Ct) = 3.10). Expression of PADI4 was elevated in only 20 (27 %) of the 74 HCC patients but decreased in 54 (73 %) of the patients. The declined PADI4 mRNA was significantly associated with Line-1 demethylation in HCC patients. PADI4 mRNA were lower in HCC patients with Line-1 ∆MI <-0.15 (Mean(-∆∆Ct) = -2.66) than those with Line-1 ∆MI >= -0.15 (Mean(-∆∆Ct) = -1.02). The results suggested that HCC showing hypomethylation of Line-1 is considered to be silencing PADI4 mRNA. And the lower PADI4 mRNA was also found in HCC patients with HBV >= 10(5) (copy/ml) than those with HBV < 10(5) (copy/ml). After treated by 5-Aza-CdR and TSA, we found that PADI4 mRNA induced significantly by TSA in Huh7 and Hep-G2 cells, but not in 7721 cells. Meanwhile, PADI4 mRNA induced by the combination of 5-Aza-CdR and TSA in HCC cells, and it could no effect for exposure to 5-Aza-CdR alone. The results suggested that decreased PADI4 mRNA is associated with global hypomethylation in HCC during HBV exposure.
Changsong Zhang; Lieying Fan; Tingting Fan; Dong Wu; Lu Gao; Yang Ling; Jing Zhu; Rong Li; Lixin Wei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-21
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  -     ISSN:  1559-0283     ISO Abbreviation:  Cell Biochem. Biophys.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.
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