SIRT3 Inhibits Cell Proliferation of Nonsmall Cell Lung Carcinoma by Inducing ROS Production

Abstract

ABSTRACT 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.

Keywords

• NSCLC
• OXPHOS
• ROS
• SIRT3
• tumor suppressor