title: HRP-3 protects the hepatoma cells from glucose deprivation-induced apoptosis.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. It is important for HCC cells to resist to apoptosis caused by adverse energy pressure in microenvironment during the HCC tumorigenesis. HRP-3, a member of hepatoma-derived growth factor (HDGF)-related proteins (HRP) family, was shown to be highly up-regulated in HCC tissues and play an important role in HCC pathogenesis based on our previous research. The aim of the study was to investigate the HRP-3's role in HCC cells endurance against energy pressure.
  
  
  METHODS
  The HRP-3 expression level in primary rat hepatocytes and human HCC cell lines were examined when changing the extracellular glucose concentration. To assess biological function of HRP-3 during glucose deprivation, HRP-3 stable knockdown and control clones of SMMC-7721 and SK-hep1 were constructed for further analysis including cellular morphology observation, apoptotic sub G1 peak analysis and the mTOR-mediated phosphorylation of S6K1 detection in the absence of glucose.
  
  
  RESULTS
  Expression level of HRP-3 protein was highly up-regulated both in primary rat hepatocytes and HCC cells as prolonging the stimulation of glucose deprivation. Both morphology and sub-G1 phase analyses indicated that stable knockdown of HRP-3 sensitized HCC cells to glucose deprivation-induced cell apoptosis. Furthermore, silence of HRP-3 prevented the de-phosphorylation of S6K1 induced by glucose deprivation, which was an essential molecular event for HCC cell survival in energy pressure.
  
  
  CONCLUSIONS
  We propose that glucose deprivation-induced HRP-3 up-regulation potentially plays a major role in protecting HCC cells against apoptosis caused by energy pressure.
authors.affiliation: The State Key Laboratory of Genetics Engineering, School of Life Science, Fudan University Shanghai 200438, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: The State Key Laboratory of Genetics Engineering, School of Life Science, Fudan UniversityShanghai 200438, P. R. China; Center for Genomic Transformational Medicine and Prevention, School of Public Health, Fudan UniversityShanghai 200032, P. R. China.
authors.forename: Deke
authors.initials: D
authors.lastname: Jiang
authors.affiliation: The Second Department of Surgery, Hospital of China No. 17 Metallurgical Construction Corp Maanshan 243000, Anhui, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qi
authors.affiliation: Center for Genomic Transformational Medicine and Prevention, School of Public Health, Fudan University Shanghai 200032, P. R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Genetics Engineering, School of Life Science, Fudan University Shanghai 200438, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.affiliation: Center for Genomic Transformational Medicine and Prevention, School of Public Health, Fudan University Shanghai 200032, P. R. China.
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003598:Cytoskeletal Proteins; D005947:Glucose / Q000172:deficiency*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D061251:Primary Cell Culture; D034622:RNA Interference; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D003598:Cytoskeletal Proteins; C498539:HDGFL3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C509210:hepatoma-derived growth factor-related protein-3, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D005947:Glucose
keywords: HRP-3; Hepatocellular carcinoma; apoptosis; glucose deprivation
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