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- Title
Decreased PADI4 mRNA Association with Global Hypomethylation in Hepatocellular Carcinoma During HBV Exposure.
- Authors
Zhang, Changsong; Fan, Lieying; Fan, Tingting; Wu, Dong; Gao, Lu; Ling, Yang; Zhu, Jing; Li, Rong; Wei, Lixin
- Abstract
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 = 1.41) than that in Non-Hcc tissues (Mean = 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 = −2.66) than those with Line-1 ∆MI >= −0.15 (Mean = −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 (copy/ml) than those with HBV < 10 (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.
- Subjects
LIVER cancer; MESSENGER RNA; CARCINOGENESIS; DEMETHYLATION; GENE expression
- Publication
Cell Biochemistry & Biophysics, 2013, Vol 65, Issue 2, p187
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1007/s12013-012-9417-3