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Decreased PADI4 mRNA Association with Global Hypomethylation in Hepatocellular Carcinoma During HBV Exposure

Cell Biochemistry and Biophysics volume 65, pages 187–195 (2013)Cite this article

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−∆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 >= 105 (copy/ml) than those with HBV < 105 (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.

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Acknowledgments

This work was supported by a grant from the Major State Basic Research Development Program of China (973 Program) (No:2010CB933900, 2010CB945600, 2011CB966200); the Natural Science Foundation of China (NO: 30901722, 30973433, 81000970, 81030041, 81072467, 31171321, 81101622); Special Funds for National key Sci-Tech Special Project of China (NO: 2012ZX10002011-011, 2012ZX10002-016); Shanghai Science and Technology Committee (Grant NO: 12ZR1439800, 10ZR1439600, 11ZR1449500, 10411963100, 10ZR1439900, 11nm0504700, 09QA1407200); Shanghai Municipal Health Bureau (Grant NO: XYQ2011044); Science Fund for Creative Research Groups, NSFC, China (NO: 30921006); the Natural Science Foundation of Jiangsu (NO: BK2011251); The Health Talents and “333” Project for Jiangsu, China (LJ201157, RC2011038, BRA2011038); and The Talents Project (“831” and health) of Changzhou.

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The authors declare that there are no conflicts of interest.

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Affiliations

  1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China

    Changsong Zhang, Dong Wu, Lu Gao, Rong Li & Lixin Wei

  2. Department of Clinical Laboratory, Shanghai East Hospital, Tongji University Medical School, No. 150, Jimo Road, Shanghai, 200120, China

    Changsong Zhang, Lieying Fan & Tingting Fan

  3. Clinical Oncology Laboratory, Changzhou Tumor Hospital, Soochow University, Huaide Road, Changzhou, 213001, China

    Changsong Zhang, Yang Ling & Jing Zhu

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  1. Changsong Zhang
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  2. Lieying Fan
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Correspondence to Lieying Fan or Lixin Wei.

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Changsong Zhang, Lieying Fan, Tingting Fan, and Dong Wu contributed equally to this study.

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Zhang, C., Fan, L., Fan, T. et al. Decreased PADI4 mRNA Association with Global Hypomethylation in Hepatocellular Carcinoma During HBV Exposure. Cell Biochem Biophys 65, 187–195 (2013). https://doi.org/10.1007/s12013-012-9417-3

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Keywords

  • Peptidylarginine deiminase type 4
  • Hepatocellular carcinoma
  • Line-1
  • Methylation