Oncometabolic role of mitochondrial sirtuins in glioma patients.

Autor: Haq MFU; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Hussain MZ; Department of Rheumatology, Military hospital, Rawalpindi, Pakistan., Mahjabeen I; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Akram Z; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Saeed N; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Shafique R; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Abbasi SF; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan., Kayani MA; Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Feb 21; Vol. 18 (2), pp. e0281840. Date of Electronic Publication: 2023 Feb 21 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0281840
Abstrakt: Mitochondrial sirtuins have diverse role specifically in aging, metabolism and cancer. In cancer, these sirtuins play dichotomous role as tumor suppressor and promoter. Previous studies have reported the involvement of sirtuins in different cancers. However, till now no study has been published with respect to mitochondrial sirtuins and glioma risks. Present study was purposed to figure out the expression level of mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) and related genes (GDH, OGG1-2α, SOD1, SOD2, HIF1α and PARP1) in 153 glioma tissue samples and 200 brain tissue samples from epilepsy patients (taken as controls). To understand the role of selected situins in gliomagenesis, DNA damage was measured using the comet assay and oncometabolic role (oxidative stress level, ATP level and NAD level) was measured using the ELISA and quantitative PCR. Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2α (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls. In case of SIRT3 (p = 0.0322), HIF1α (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed. ROC curve analysis and cox regression analysis showed the good diagnostic and prognostic value of mitochondrial sirtuins in glioma patients. Oncometabolic rate assessment analysis showed significant increased ATP level (p<0.0001), NAD+ level [(NMNAT1 (p<0.0001), NMNAT3 (p<0.0001) and NAMPT (p<0.04)] and glutathione level (p<0.0001) in glioma patients compared to controls. Significant increased level of damage ((p<0.04) and decrease level of antioxidant enzymes include superoxide dismutase (SOD, p<0.0001), catalase (CAT, p<0.0001) and glutathione peroxidase (GPx, p<0.0001) was observed in patients compared to controls. Present study data suggest that variation in expression pattern of mitochondrial sirtuins and increased metabolic rate may have diagnostic and prognostic significance in glioma patients.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Haq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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