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Sirtuin Family Members Selectively Regulate Autophagy in Osteosarcoma and Mesothelioma Cells in Response to Cellular

Richa Garva1, Chutamas Thepmalee2,3, Umpa Yasamut4

  • 1Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.

Frontiers in Oncology
|October 15, 2019
PubMed

Insights

Mitochondrial sirtuins (SIRT3 and SIRT5) promote cell survival by regulating autophagy under stress. SIRT1

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Sirtuins (SIRTs) are NAD+-dependent deacetylases linking gene regulation to cellular stress responses.
  • Understanding sirtuin roles in autophagy is crucial for cellular fate determination.

Purpose of the Study:

  • Investigate the roles of SIRT1, SIRT3, and SIRT5 in autophagy regulation under stress.
  • Determine sirtuin contributions to cell survival in osteosarcoma and mesothelioma cells.

Main Methods:

  • Silencing of sirtuin genes (SIRT1, SIRT3, SIRT5).
  • Exposure of human cancer cells to DNA damage and oxidative stress.
  • Monitoring cell survival and autophagy markers.

Main Results:

  • Mitochondrial sirtuins SIRT3 and SIRT5 are pro-proliferative and positively regulate autophagy under stress.
  • SIRT1 exhibits context-dependent, cell-specific roles in autophagy modulation.
  • SIRT3 and SIRT5 impact early and late autophagy stages; SIRT1 primarily affects later stages.
  • SIRT5 plays a key role in regulating SIRT3 and SIRT1 activity through feedback loops.

Conclusions:

  • Sirtuin family members have distinct roles in autophagy regulation in different cancer cell types.
  • Differential sirtuin functions in autophagy under stress offer potential therapeutic strategies for cancer treatment.
Keywords:
LC3autophagybeclin-1mesotheliomaosteosarcomasirtuinstranscription

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