SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis
Journal
Annals of Surgical Oncology
Journal Volume
19
Journal Issue
6
Pages
2011-2019
Date Issued
2012
Author(s)
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 a-fetoprotein level, higher tumor grade, and absence of b-catenin mutation. SIRT1 expression predicted poor longterm 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. ? 2012 Society of Surgical Oncology.
SDGs
Other Subjects
alpha fetoprotein; antineoplastic agent; beta catenin; messenger RNA; proteasome; sirtuin 1; sorafenib; ubiquitin; adult; article; cancer chemotherapy; cancer grading; cancer patient; cancer resistance; carcinogenesis; controlled study; female; gene mutation; half life time; histopathology; human; human cell; human tissue; immunohistochemistry; liver cell carcinoma; major clinical study; male; prediction; prognosis; protein expression; protein metabolism; survival time; Adolescent; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antibiotics, Antineoplastic; Antineoplastic Agents; Benzenesulfonates; beta Catenin; Blotting, Western; Carcinoma, Hepatocellular; Cell Proliferation; Cells, Cultured; Doxorubicin; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Half-Life; Humans; Immunoenzyme Techniques; Immunoprecipitation; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Staging; Prognosis; Proteolysis; Pyridines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sirtuin 1; Survival Rate; Tumor Markers, Biological; Young Adult
Type
journal article