title: SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis.
abstract: BACKGROUND
  SIRT1 is a NAD+-dependent deacetylase that plays crucial roles in many biological processes, including stress response, apoptosis, cellular metabolism, adaptation to calorie restriction, aging, and tumorigenesis. The purpose of this study is to elucidate the clinicopathological and functional significance of SIRT1 expression in hepatocellular carcinoma (HCC).
  
  
  METHODS
  SIRT1 expression in HCC was determined by immunohistochemical staining. The results were correlated with clinicopathological parameters. SIRT1 was overexpressed in HCC cell line SK-Hep1 to study its role in tumorigenesis and resistance to chemotherapy.
  
  
  RESULTS
  SIRT1 was overexpressed in 95 of 172 HCCs (55%). SIRT1 overexpression was associated with higher α-fetoprotein level, higher tumor grade, and absence of β-catenin mutation. SIRT1 expression predicted poor long-term survival for patients with resected HCC. The elevated SIRT1 protein level in HCC was not attributable to the elevation of mRNA level. The half-life of SIRT1 protein was longer in cell lines with higher expression of SIRT1. We further demonstrated that SIRT1 was degraded by the 26S proteasome in an ubiquitin-dependent manner. Overexpression of SIRT1 promoted tumorigenesis and resistance to chemotherapeutical agent and sorafenib.
  
  
  CONCLUSIONS
  SIRT1 is an oncogenic protein for HCC and is a predictor of worse outcome after surgical resection of HCC.
authors.affiliation: Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsieh-Cheng
authors.initials: HC
authors.lastname: Chen
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D059748:Proteolysis; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D000077157:Sorafenib; D015996:Survival Rate; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D051176:beta Catenin; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib; C447939:SIRT1 protein, human; D056564:Sirtuin 1