Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma
- 205 Downloads
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.
KeywordsHepatocellular carcinoma PIDD Proliferation Apoptosis
This work was supported by the National Natural Scientific Foundation of China (no. 81272708).
Compliance with ethical standards
Conflicts of interest
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.
- 15.Heikaus S, Pejin I, Gabbert HE, Ramp U, Mahotka C. Piddosome expression and the role of caspase-2 activation for chemotherapy-induced apoptosis in RCCs. Cell Oncol Off J Int Soc Cell Oncol. 2010;32:29–42.Google Scholar
- 21.Inagawa S, Itabashi M, Adachi S, Kawamoto T, Hori M, Shimazaki J, et al. Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival. Clin Cancer Res Off J Am Assoc Cancer Res. 2002;8:450–6.Google Scholar
- 23.Kitamoto M, Nakanishi T, Kira S, Kawaguchi M, Nakashio R, Suemori S, et al. The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis. Cancer. 1993;72:1859–65.CrossRefPubMedGoogle Scholar