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Tumor Biology

, Volume 37, Issue 8, pp 10447–10457 | Cite as

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma

  • Weidong Shi
  • Wei Huang
  • Yuyan Chen
  • Shusen Zhang
  • Pan Xu
  • Xiaoling Gu
  • Hui Fan
  • Jian Xu
  • Yongmei Chen
  • Runzhou Ni
  • Cuihua Lu
  • Xiubing Zhang
Original Article

Abstract

p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.

Keywords

Hepatocellular carcinoma PIDD Proliferation Apoptosis 

Notes

Acknowledgments

This work was supported by the National Natural Scientific Foundation of China (no. 81272708).

Compliance with ethical standards

Conflicts of interest

None

Ethics approval and consent to participate

All HCC specimens were collected in accordance with the protocols approved by the Ethics Committee of Affiliated Hospital of Nantong University, and every patient submitted written informed consent.

Supplementary material

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ESM 1

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High resolution image (TIF 1460 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Weidong Shi
    • 2
  • Wei Huang
    • 1
  • Yuyan Chen
    • 3
  • Shusen Zhang
    • 1
  • Pan Xu
    • 4
  • Xiaoling Gu
    • 4
  • Hui Fan
    • 2
  • Jian Xu
    • 2
  • Yongmei Chen
    • 2
  • Runzhou Ni
    • 1
  • Cuihua Lu
    • 1
  • Xiubing Zhang
    • 2
  1. 1.Department of Gastroenterology, Affiliated Hospital of Nantong UniversityNantong UniversityNantongChina
  2. 2.Department of Medical Oncology, Second People’s Hospital of Nantong CityNantong UniversityNantongChina
  3. 3.Class 5, Grade 13, Clinical Medicine, Medical CollegeNantong UniversityNantongChina
  4. 4.Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Information and Molecular Drug TargetNantong UniversityNantongChina

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