Digestive Diseases and Sciences

, Volume 62, Issue 8, pp 1872–1880 | Cite as

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


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.


Hepatocellular carcinoma Metabolism SIRT-3 Tumor suppressor 





Superoxide dismutase 2


Hepatocellular carcinoma


Hepatitis B virus


Hepatitis C virus


Autoimmune hepatitis


Primary biliary cholangitis


Nonalcoholic steatohepatitis


Type 2 diabetes mellitus


Nonalcoholic fatty liver disease


Superoxide dismutase 2


Oral squamous cell carcinoma


Nicotinamide mononucleotide adenylyltransferase 2


Gastric cancer


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



The authors thank Grainne Tierney for editing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.


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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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