Sun Xiaodan, Wang Shouhan, Li Qingchang
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of 2nd Gynecologic Oncology Surgery, Jilin Cancer Hospital, Changchun, China.
Front Genet. 2019 Sep 13;10:879. doi: 10.3389/fgene.2019.00879. eCollection 2019.
Sirtuins (SIRTs) 1-7 are a family of intracellular enzymes, which possess nicotinamide adenine dinucleotide-dependent deacetylase activity. Emerging evidence suggest that SIRTs play vital roles in tumorigenesis by regulating energy metabolism, DNA damage repair, genome stability, and other cancer-associated cellular processes. However, the distinct roles of the seven members in ovarian cancer (OC) remain elusive. The transcriptional expression patterns, prognostic values, and genetic alterations of seven SIRTs in OC patients were investigated in this study using a range of databases: Oncomine and Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, the Cancer Genome Atlas, and cBioPortal. The protein-protein interaction networks of SIRTs were assessed in the String database. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed in Database for Annotation, Visualization, and Integrated Discovery. The mRNA expression levels of SIRT1-4 and 7 were downregulated, while that of SIRT5 was upregulated and SIRT6 exhibited both expression dysregulation in patients with OC. Dysregulated SIRTs mRNA expression levels were associated with prognosis. Moreover, genetic alterations primarily occurred in SIRT2, 5, and 7. Network analysis indicated that SIRTs and their 20 interactors were associated with tumor-related pathways. This comprehensive bioinformatics analysis revealed that SIRT1-4, 6, and 7 may be new prognostic biomarkers, while SIRT5 is a potential target for accurate therapy for patients with OC, but further studies are needed to confirm this notion. These findings will contribute to a better understanding of the distinct roles of SIRTs in OC.
沉默调节蛋白（SIRTs）1 - 7是一类细胞内酶家族，具有烟酰胺腺嘌呤二核苷酸依赖性脱乙酰酶活性。新出现的证据表明，SIRTs通过调节能量代谢、DNA损伤修复、基因组稳定性及其他与癌症相关的细胞过程，在肿瘤发生中发挥重要作用。然而，这七个成员在卵巢癌（OC）中的不同作用仍不清楚。本研究使用一系列数据库：Oncomine和基因表达谱交互分析、Kaplan - Meier绘图仪、癌症基因组图谱和cBioPortal，调查了OC患者中七种SIRTs的转录表达模式、预后价值和基因改变。在String数据库中评估了SIRTs的蛋白质 - 蛋白质相互作用网络。在注释、可视化和综合发现数据库中分析了基因本体富集和京都基因与基因组百科全书通路。OC患者中SIRT1 - 4和7的mRNA表达水平下调，而SIRT5的表达上调，SIRT6表现出表达失调。SIRTs mRNA表达水平失调与预后相关。此外，基因改变主要发生在SIRT2、5和7中。网络分析表明，SIRTs及其20个相互作用分子与肿瘤相关通路有关。这项全面的生物信息学分析表明，SIRT1 - 4、6和7可能是新的预后生物标志物，而SIRT5是OC患者精准治疗的潜在靶点，但需要进一步研究来证实这一观点。这些发现将有助于更好地理解SIRTs在OC中的不同作用。
