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Tumor Biology

, Volume 36, Issue 6, pp 4063–4074 | Cite as

Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target

  • Yuting Wu
  • Xiaoming Meng
  • Cheng Huang
  • Jun Li
Review

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent neoplasms worldwide, ranking as the second leading cause of cancer-related death due to its high invasive and metastatic potential. SIRT1 (silent information regulator 1), a member of mammalian sirtuin family protein (SIRT1–SIRT7), functions as a conserved nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase to implicate in the modulation of transcriptional silencing and cell survival. Recently, except for the regulatory role of SIRT1 in various biological processes, the carcinogenesis effect of SIRT1 was revealed in HCC. Importantly, SIRT1 was confirmed to be involved in tumorigenesis, metastasis, prognosis, and chemical resistant of HCC, as a result of its deacetylation of oncogenic or tumor suppressor factors. The focus of this review was to delineate the carcinogenesis effects of SIRT1 on HCC and present an overview of SIRT1 functions in normal liver followed by SIRT1 roles in HCC, with focus on the underlying molecular mechanism to promote SIRT1 as a new therapeutic target for HCC.

Keywords

Silent information regulator 1 (SIRT1) Hepatocellular carcinoma (HCC) Proliferation Apoptosis Therapies 

Abbreviations

SIRT1

Silent information regulator 1

HCC

Hepatocellular carcinoma

PGC1-α

Peroxisome proliferator-activated receptor-γ coactivator 1α

PPAR-γ

Peroxisome proliferator-activated receptor-γ

LXR

Liver X receptor

FXR

Farnesoid X receptor

SREBP

Sterol regulatory element-binding protein

FOXO

Forkhead box O

NF-kB

Nuclear factor-κB

c-Myc

Cellular homologue of avian myelocytomatosis virus oncogene

HIFs

Hypoxia-inducible transcription factors

Atg

Autophagy-related gene

NAFLD

Nonalcoholic fatty liver disease

NAD

Nicotinamide adenine dinucleotide

Af

Archaeoglobus fulgidus

Cys

Cysteine

CR

Caloric restriction

CRTC2

CREB-regulated transcription coactivator 2

PPARa

Peroxisome proliferator-activated receptor a

ER

Endoplasmic reticulum

ABCA1

ATP-binding cassette transporter A1

HNF1α

Hepatocyte nuclear factor 1α

Per2

Period gene 2

HBV

Hepatitis B virus

MPT

Mouse proximal tubular

SP-1

Specificity protein-1

u-PA

Urokinase-type plasminogen activator

miRNAs

MicroRNAs

3′UTR

3′-Untranslated region

CSCs

Cancer stem cells

FASN

Fatty acid synthase

HMGCR

Hydroxy-3-methyl-glutaryl-coa reductase

EMT

Epithelial to mesenchymal transition

AMPK

AMP-activated protein kinase

hTERT

Human telomerase reverse transcriptase

hTERC

Human telomerase RNA component

TRF

Telomeric repeat-binding factors

POT1

Protection of telomeres 1

TIN2

TRF1-interacting protein 2

TPP1

POT1-TIN2 organizing protein

Rap1

Repressor/activator protein 1

YAP

Yes-associated protein

TEAD4

TEA domain family member 4

PTEN

Phosphatase and tensin homologue deleted on chromosome 10

PI3K

Phosphatidylinositol 3 kinase

AKT

Protein kinase B

PDK-1

3-Phosphoinositide-dependent protein kinase-1

APO10LA

Apo-100-lycopenoic acid

IκB

Inhibitor of NF-κB

IKK

IκB kinase

Notes

Acknowledgments

This project was supported by the National Science Foundation of China (No. 81473268, No. 81273526) and Anhui Science and Technology research projects (No. 1301042212)

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yuting Wu
    • 1
    • 2
  • Xiaoming Meng
    • 1
    • 2
  • Cheng Huang
    • 1
    • 2
  • Jun Li
    • 1
    • 2
  1. 1.School of PharmacyAnhui Medical UniversityHefeiChina
  2. 2.Institute for Liver DiseasesAnhui Medical University (AMU)HefeiChina

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