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

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM Clinical Respiratory Journal Pub Date : 2024-11-05 DOI:10.1111/crj.70033

Ze Yu, Hongtao Liao, Guanhuai Wu, Ying Liu, Guoqiang Zhang, Liang Xiao, Shuibo Yang, Jia Liu, Guocai Yang

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引用次数: 0

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.

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SIRT3 通过诱导 ROS 生成抑制非小细胞肺癌细胞增殖

背景：Sirtuin 3（SIRT3）位于线粒体基质中，调节代谢酶的乙酰化水平。作为癌基因或抑癌基因，SIRT3 在某些癌症的发生和发展过程中发挥着重要作用。本研究探讨了 SIRT3 在非小细胞肺癌（NSCLC）进展过程中的作用：本研究采用生物信息学方法分析了SIRT3在NSCLC组织和正常组织中的差异表达、预后、单细胞分析以及相关信号通路。构建了过表达SIRT3的慢病毒，用CCK8和集落形成试验评估NSCLC细胞的增殖，用流式细胞术检测ROS的产生，用海马试验测量细胞耗氧量（OCR）：结果：SIRT3在NSCLC中的表达明显下降，而SIRT3的低表达与预后不良密切相关。此外，从整体上看，SIRT3的上调通过增加氧化磷酸化（OXPHOS）和ROS的产生抑制了A549和SK-MES-1细胞的增殖：总之，我们的研究结果表明，SIRT3 是一种肿瘤抑制因子，可通过刺激 ROS 生成抑制 NSCLC 的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)