title: Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma.
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.
authors: Department of Medical Oncology, Second People's Hospital of Nantong City, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Weidong
authors: W
authors: Shi
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Wei
authors: W
authors: Huang
authors: Class 5, Grade 13, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Yuyan
authors: Y
authors: Chen
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Shusen
authors: S
authors: Zhang
authors: Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Information and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Pan
authors: P
authors: Xu
authors: Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Information and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Xiaoling
authors: X
authors: Gu
authors: Department of Medical Oncology, Second People's Hospital of Nantong City, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Hui
authors: H
authors: Fan
authors: Department of Medical Oncology, Second People's Hospital of Nantong City, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Jian
authors: J
authors: Xu
authors: Department of Medical Oncology, Second People's Hospital of Nantong City, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Yongmei
authors: Y
authors: Chen
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors: Runzhou
authors: R
authors: Ni
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. lch670608@sina.com.
authors: Cuihua
authors: C
authors: Lu
authors: Department of Medical Oncology, Second People's Hospital of Nantong City, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. zhangxiubing2015@163.com.
authors: Xiubing
authors: X
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D009363:Neoplasm Proteins; C485896:PIDD1 protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins
keywords: Apoptosis; Hepatocellular carcinoma; PIDD; Proliferation