Digestive Diseases and Sciences

, Volume 62, Issue 8, pp 1872–1880

Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma

  • Serena De Matteis
  • Anna Maria Granato
  • Roberta Napolitano
  • Chiara Molinari
  • Martina Valgiusti
  • Daniele Santini
  • Francesco Giuseppe Foschi
  • Giorgio Ercolani
  • Umberto Vespasiani Gentilucci
  • Luca Faloppi
  • Mario Scartozzi
  • Giovanni Luca Frassineti
  • Andrea Casadei Gardini
Review

Abstract

Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD+)-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC). SIRT-3 regulatory effect and involvement in metabolism dysfunctions may have strong implications in HCC development and treatment. Research literature widely reports the relationship between metabolic disorders and HCC development. This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection.

Keywords

Hepatocellular carcinoma Metabolism SIRT-3 Tumor suppressor 

Abbreviations

SIRT

Sirtuin

SOD2

Superoxide dismutase 2

HCC

Hepatocellular carcinoma

HBV

Hepatitis B virus

HCV

Hepatitis C virus

AIH

Autoimmune hepatitis

PBC

Primary biliary cholangitis

NASH

Nonalcoholic steatohepatitis

DM2

Type 2 diabetes mellitus

NAFLD

Nonalcoholic fatty liver disease

MnSOD

Superoxide dismutase 2

OSCC

Oral squamous cell carcinoma

NMNAT2

Nicotinamide mononucleotide adenylyltransferase 2

GC

Gastric cancer

MIAM

2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Serena De Matteis
    • 1
  • Anna Maria Granato
    • 2
  • Roberta Napolitano
    • 1
  • Chiara Molinari
    • 1
  • Martina Valgiusti
    • 3
  • Daniele Santini
    • 4
  • Francesco Giuseppe Foschi
    • 5
  • Giorgio Ercolani
    • 6
    • 7
  • Umberto Vespasiani Gentilucci
    • 8
  • Luca Faloppi
    • 9
  • Mario Scartozzi
    • 9
  • Giovanni Luca Frassineti
    • 3
  • Andrea Casadei Gardini
    • 3
  1. 1.Biosciences LaboratoryIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  2. 2.Immunotherapy and Cell Therapy UnitIRST IRCCSMeldolaItaly
  3. 3.Department of Medical OncologyIRST IRCCSMeldolaItaly
  4. 4.Campus Bio-MedicoUniversity of RomeRomeItaly
  5. 5.Department of Internal MedicineOspedale per gli InfermiFaenzaItaly
  6. 6.Department of General SurgeryMorgagni-Pierantoni HospitalForlìItaly
  7. 7.Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
  8. 8.Internal Medicine and Hepatology UnitUniversity Campus Bio-MedicoRomeItaly
  9. 9.Medical Oncology, University HospitalUniversity of CagliariMonserrato, CagliariItaly

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