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PPPDE1 promotes hepatocellular carcinoma development by negatively regulate p53 and apoptosis

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Abstract

We have previously identified that PPPDE1 is a deubiquitinase (DUB) belonging to a cysteine isopeptidase family. Here we sought to explore the biological significance of PPPDE1 in hepatocellular carcinoma and its underlying molecular mechanism. In the present study, we found that amplification and overexpression of PPPDE1 were associated with poor prognosis in hepatocellular carcinoma (HCC). We also demonstrated that knocking down of PPPDE1 could significantly block the clonal growth and tumorigenicity of human HCC cells, which revealed a critical role for PPPDE1 in HCC development. Furthermore, we proved that PPPDE1 is a key modulator of p53 protein level and its down stream apoptosis pathway. Taken together, these results suggested that PPPDE1 is a putative HCC driver gene and extensive studies should be conducted in the future to investigate the role of PPPDE1 in HCC and other tumors.

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Abbreviations

DUBs:

Deubiquitinating enzymes

PPPDE:

After Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81201569, No. 81541151), the Beijing Natural Science Foundation (No. 7132186) and the National Key Sci-Tech Special Project of China (No. 2018ZX10302207, No. 2017ZX10203202).

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Authors and Affiliations

  1. Chinese Center for Disease Control and Prevention, Beijing, 102206, China

    Xingwang Xie & Yu Wang

  2. Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Beijing, 100044, China

    Xingwang Xie, Xueyan Wang, Ran Fei, Nan Wu, Xu Cong, Lai Wei & Hongsong Chen

  3. Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China

    Weijia Liao & Qian Chen

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  1. Xingwang Xie
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  2. Xueyan Wang
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  3. Weijia Liao
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  4. Ran Fei
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  5. Nan Wu
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  6. Xu Cong
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  8. Lai Wei
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  9. Yu Wang
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  10. Hongsong Chen
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Correspondence to Yu Wang or Hongsong Chen.

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Xie, X., Wang, X., Liao, W. et al. PPPDE1 promotes hepatocellular carcinoma development by negatively regulate p53 and apoptosis. Apoptosis 24, 135–144 (2019). https://doi.org/10.1007/s10495-018-1491-6

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