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

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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.

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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

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Acknowledgment

The authors thank Grainne Tierney for editing the manuscript.

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Authors and Affiliations

  1. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli, 40, 47014, Meldola, Italy

    Serena De Matteis, Roberta Napolitano & Chiara Molinari

  2. Immunotherapy and Cell Therapy Unit, IRST IRCCS, Via Maroncelli, 40, 47014, Meldola, Italy

    Anna Maria Granato

  3. Department of Medical Oncology, IRST IRCCS, Via Maroncelli, 40, 47014, Meldola, Italy

    Martina Valgiusti, Giovanni Luca Frassineti & Andrea Casadei Gardini

  4. Campus Bio-Medico, University of Rome, Via Àlvaro del Portillo, 21, 00128, Rome, Italy

    Daniele Santini

  5. Department of Internal Medicine, Ospedale per gli Infermi, Viale Stradone, 9, 48018, Faenza, Italy

    Francesco Giuseppe Foschi

  6. Department of General Surgery, Morgagni-Pierantoni Hospital, Via Carlo Forlanini, 34, 47121, Forlì, Italy

    Giorgio Ercolani

  7. Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy

    Giorgio Ercolani

  8. Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Via Àlvaro del Portillo, 21, 00128, Rome, Italy

    Umberto Vespasiani Gentilucci

  9. Medical Oncology, University Hospital, University of Cagliari, SS 554 km 4.500, Monserrato, Cagliari, Italy

    Luca Faloppi & Mario Scartozzi

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  1. Serena De Matteis
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  2. Anna Maria Granato
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  3. Roberta Napolitano
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Correspondence to Serena De Matteis.

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De Matteis, S., Granato, A.M., Napolitano, R. et al. Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma. Dig Dis Sci 62, 1872–1880 (2017). https://doi.org/10.1007/s10620-017-4615-x

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