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SIRT5 下调与胶质母细胞瘤的不良预后相关。

SIRT5 downregulation is associated with poor prognosis in glioblastoma.

机构信息

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

出版信息

Cancer Biomark. 2019;24(4):449-459. doi: 10.3233/CBM-182197.

DOI:10.3233/CBM-182197
PMID:30909186
Abstract

OBJECTIVE

Sirtuins (SIRT) are NAD+-dependent protein deacetylases that are involved in the regulation of cancer-associated pathways. However, the biological role of these deacetylases remains elusive in glioblastoma (GBM). Here, we evaluated the effects of 7 sirtuins regarding their occurrence and prognostic value for GBM.

METHODS

In this research, the effects of SIRT5 on the occurrence and prognosis of GBM were evaluated using integrative bioinformatics analyses.

RESULTS

Based on comprehensive analyses of data obtained from web-based bioinformatics platforms, the data demonstrate that only SIRT5 expression is statistically decreased in GBM tissues. The clinical relevance analysis shows that downregulation of SIRT5 is significantly correlated with a shorter survival time. Moreover, the expression levels of SIRT5 were confirmed to be negatively associated with DNA methylation status. In addition, a protein-protein interaction network was constructed to determine the relationship of genes coexpressed with SIRT5. Functional enrichment analysis revealed that SIRT5 was potentially involved in epithelial-mesenchymal transition and in regulating cell communications.

CONCLUSIONS

Collectively, our results indicate that SIRT5 acts as a potential suppresser during tumorigenesis, and suggest that SIRT5 may be a promising prognostic biomarker of GBM.

摘要

目的

沉默信息调节因子 2 相关酶 1(SIRT)是一种 NAD+依赖的蛋白去乙酰化酶,参与调控与癌症相关的通路。然而,这些去乙酰化酶在胶质母细胞瘤(GBM)中的生物学作用仍不清楚。在这里,我们评估了 7 种 SIRT 对 GBM 发生和预后的影响。

方法

在这项研究中,使用整合生物信息学分析评估了 SIRT5 对 GBM 发生和预后的影响。

结果

基于对来自网络生物信息学平台的数据的综合分析,数据表明只有 SIRT5 的表达在 GBM 组织中统计学上降低。临床相关性分析表明,SIRT5 的下调与较短的生存时间显著相关。此外,SIRT5 的表达水平与 DNA 甲基化状态呈负相关。此外,构建了蛋白质-蛋白质相互作用网络来确定与 SIRT5 共表达的基因之间的关系。功能富集分析表明,SIRT5 可能参与上皮-间充质转化和调节细胞通讯。

结论

综上所述,我们的结果表明 SIRT5 在肿瘤发生过程中起潜在的抑制作用,并表明 SIRT5 可能是 GBM 有前途的预后生物标志物。

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