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SIRT3 Inhibits Cell Proliferation of Nonsmall Cell Lung Carcinoma by Inducing ROS Production
Ze Yu1,2, Hongtao Liao3, Guanhuai Wu3
1Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital, Zhejiang University School of Medicine, Zhoushan, Zhejiang, China.
Background:
Sirtuin 3 (SIRT3) is located in the mitochondrial matrix, regulating acetylation levels of metabolic enzymes. As an oncogene or a tumor suppressor gene, SIRT3 plays an important role in the commencement and progression of certain cancers. In this research, we investigated the role of SIRT3 in the progression of nonsmall cell lung carcinoma (NSCLC).
Methods:
In this study, bioinformatics was used to analyze the differential expression of SIRT3 in NSCLC tissue and normal tissues, prognosis, single-cell analysis, and related signaling pathways. The Lentiviral overexpressing SIRT3 was constructed, and CCK8 and colony formation assay were used to evaluate the NSCLC cells proliferation, ROS production was detected by flow cytometry, and the sea-horse test was used to measure cellular oxygen consumption (OCR).
Results:
SIRT3 expression was significantly decreased in NSCLC, and low expression of SIRT3 was closely related to the poor prognosis. Besides, on the whole, upregulation of SIRT3 suppressed cell proliferation in A549 and SK-MES-1 cells via increasing oxidative phosphorylation (OXPHOS) and ROS production.
Conclusions:
Overall, our findings suggested that SIRT3 functions as a tumor suppressor that can suppress the progression of NSCLC via stimulating ROS production.
Insights
Sirtuin 3 (SIRT3) acts as a tumor suppressor in nonsmall cell lung carcinoma (NSCLC). Upregulating SIRT3 inhibits NSCLC cell proliferation by increasing oxidative phosphorylation and ROS production, suggesting a poor prognosis with low SIRT3 expression.
Area of Science:
- Mitochondrial biology
- Cancer research
- Molecular oncology
Background:
- Sirtuin 3 (SIRT3) is a mitochondrial matrix enzyme regulating metabolic enzyme acetylation.
- SIRT3 can function as either an oncogene or a tumor suppressor, influencing cancer initiation and progression.
- This study focuses on the specific role of SIRT3 in nonsmall cell lung carcinoma (NSCLC) progression.
Purpose of the Study:
- To investigate the role of Sirtuin 3 (SIRT3) in the progression of nonsmall cell lung carcinoma (NSCLC).
- To analyze the differential expression and prognostic significance of SIRT3 in NSCLC.
- To elucidate the mechanisms by which SIRT3 influences NSCLC cell behavior.
Main Methods:
- Bioinformatic analysis of SIRT3 expression, prognosis, single-cell data, and signaling pathways in NSCLC.
- Construction of lentiviral vectors for SIRT3 overexpression.
- Assessment of NSCLC cell proliferation using CCK8 and colony formation assays.
- Detection of reactive oxygen species (ROS) production via flow cytometry.
- Measurement of cellular oxygen consumption (OCR) using Seahorse assays.
Main Results:
- SIRT3 expression is significantly decreased in NSCLC tissues compared to normal tissues.
- Low SIRT3 expression is correlated with a poor prognosis in NSCLC patients.
- Overexpression of SIRT3 suppressed proliferation in NSCLC cell lines (A549, SK-MES-1).
- SIRT3 upregulation increased oxidative phosphorylation (OXPHOS) and ROS production in NSCLC cells.
Conclusions:
- SIRT3 functions as a tumor suppressor in nonsmall cell lung carcinoma.
- SIRT3 suppresses NSCLC progression, potentially through the stimulation of ROS production.
- Targeting SIRT3 may represent a therapeutic strategy for NSCLC.
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