SIRT5 Promotes Cisplatin Resistance in Ovarian Cancer by Suppressing DNA Damage in a ROS-Dependent Manner via Regulation of the Nrf2/HO-1 Pathway
Open Access
- 13 August 2019
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 9, 754
- https://doi.org/10.3389/fonc.2019.00754
Abstract
Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance in vitro. Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.Keywords
Funding Information
- National Natural Science Foundation of China (81672964, 81702269, 81874214)
This publication has 64 references indexed in Scilit:
- Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic FunctionsPLOS ONE, 2013
- Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective AutophagyMolecular Cell, 2013
- Resveratrol Induces Premature Senescence in Lung Cancer Cells via ROS-Mediated DNA DamagePLOS ONE, 2013
- SIRT5: A Safeguard Against Oxidative Stress-Induced Apoptosis in CardiomyocytesCellular Physiology and Biochemistry, 2013
- Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and DesuccinylaseScience, 2011
- The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1Nature, 2010
- SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea CycleCell, 2009
- Opposing Effects of Sirtuins on Neuronal Survival: SIRT1-Mediated Neuroprotection Is Independent of Its Deacetylase ActivityPLOS ONE, 2008
- Heme Oxygenase-1 in Tumors: Is It a False Friend?Antioxidants and Redox Signaling, 2007
- Cisplatin: mode of cytotoxic action and molecular basis of resistanceOncogene, 2003