Frontiers in Nutrition (Sep 2019)

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

  • Marius Farcas,
  • Marius Farcas,
  • Andrei-Alexandru Gavrea,
  • Andrei-Alexandru Gavrea,
  • Diana Gulei,
  • Calin Ionescu,
  • Calin Ionescu,
  • Alexandru Irimie,
  • Alexandru Irimie,
  • Cristina S. Catana,
  • Ioana Berindan-Neagoe,
  • Ioana Berindan-Neagoe,
  • Ioana Berindan-Neagoe

DOI
https://doi.org/10.3389/fnut.2019.00148
Journal volume & issue
Vol. 6

Abstract

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Current treatment options for inoperable HCCs have decreased therapeutic efficacy and are associated with systemic toxicity and chemoresistance. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide–dependent enzyme that is frequently overexpressed in HCC, where it promotes tumorigenicity, metastasis, and chemoresistance. SIRT1 also maintains the tumorigenic and self-renewal proprieties of liver cancer stem cells. Multiple tumor-suppressive microRNAs (miRNAs) are downregulated in HCC and, as a consequence, permit SIRT1-induced tumorigenicity. However, either directly targeting SIRT1, combining conventional chemotherapy with SIRT1 inhibitors, or upregulating tumor-suppressive miRNAs may improve therapeutic efficacy and patient outcomes. Here, we present the interaction between SIRT1, miRNAs, and liver cancer stem cells and discuss the consequences of their interplay for the development and treatment of HCC.

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