山西医科大学学报2024，Vol.55Issue(7)：820-827,8.DOI:10.13753/j.issn.1007-6611.2024.07.002
SIRT3在皮肤鳞状细胞癌中的作用
Role of SIRT3 in skin squamous cell carcinoma
摘要
Abstract
Objective To investigate the effects of Sirtuin-3(SIRT3)on skin squamous cell carcinoma(SCC)and its potential regula-tory mechanism.Methods The expression of SIRT3 in various tumors was analyzed using the Gene Expression Profiling Interactive Analysis(GEPIA)database.A431 cell line was transfected with SIRT3 small interfering RNA(siRNA)to construct SIRT3 knockdown cells(si-SIRT3 group),and A431 cell line was transfected with negative control siRNA as control group.RT-qPCR and Western blot were used to detect SIRT3 mRNA and protein levels.Flow cytometry was employed to measure the apoptosis rate,the reactive oxygen species(ROS)level,and the mitochondrial membrane potential(MMP).Western blot was also applied to detect the expression of the apoptotic protein Bax,cytochrome C protein,and the anti-apoptotic protein Bcl-2.CCK-8 assay was used to assess the proliferation rate.A431 cells were treated with a SIRT3 inhibitor 3-TYP and an equal amount of DMSO,respectively,and then the apoptosis rate was detected by flow cytometry.Differentially expressed genes between control group and si-SIRT3 group were identified by transcrip-tome sequencing analysis,and analyzed by GO and KEGG enrichment analysis.Results SIRT3 expression was upregulated in thymoma and diffuse large B-cell lymphoma(P＜0.05).Compared with control group,the apoptosis rate was significantly increased in si-SIRT3 group(P＜0.01),ROS release was elevated(P＜0.05),MMP was significantly reduced(P＜0.001),the expressions of Bax and cytochrome C protein were upregulated,the expression of Bcl-2 was downregulated,and the cell proliferation was inhibited(P＜0.001).The apoptosis rate in 3-TYP group was also increased compared to control group(P＜0.001).Transcriptome sequencing analysis revealed 94 differentially expressed genes between control group and si-SIRT3 group,including 59 upregulated genes and 35 downregulated genes.These genes were primarily enriched in signaling pathways related to metabolism,signal transduction,calcium ion regulation,protein transport,proteolysis,extracellular matrix,metallopeptidases,and hormone secretion.Conclusion Downregulation of SIRT3 expression in skin squamous cell carcinoma cells can promote the cell apoptosis,inhibit the cell proliferation,and SIRT3 is expected to be a new therapeutic target for patients with skin squamous cell carcinoma.关键词
皮肤鳞癌/SIRT3/活性氧/细胞凋亡/线粒体膜电位Key words
skin squamous cell carcinoma/SIRT3/reactive oxygen species/cell apoptosis/mitochondrial membrane potential分类
医药卫生引用本文复制引用
魏艳,王丽娟,周艳,郑焱..SIRT3在皮肤鳞状细胞癌中的作用[J].山西医科大学学报,2024,55(7):820-827,8.基金项目
国家自然科学基金项目(81972938) （81972938）
陕西省科技重点基金资助项目(2015KTCL03-10) （2015KTCL03-10）
陕西省自然科学基础研究计划项目(2024JC-YBQN-0783) （2024JC-YBQN-0783）
西安交通大学第一附属医院科研发展基金项目(2022QN-12) （2022QN-12）
