通过整合生物信息学分析鉴定阿司匹林联合立普妥治疗前列腺癌的靶点及通路。

Identification of target and pathway of aspirin combined with Lipitor treatment in prostate cancer through integrated bioinformatics analysis.

机构信息

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City 529020, China.

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Toxicol Appl Pharmacol. 2022 Oct 1;452:116169. doi: 10.1016/j.taap.2022.116169. Epub 2022 Aug 1.

DOI:10.1016/j.taap.2022.116169

PMID:35926565

Abstract

PURPOSE

Our previous studies have confirmed that aspirin combined with Lipitor inhibited the development of prostate cancer (PCa), but the mechanisms need to be comprehensively expounded. The study aims to screen out the hub genes of combination therapy and to explore their association with the pathogenesis and prognosis of PCa.

METHODS

Gene expressions were quantified by RNA sequencing (RNA-seq). Altered biological function, pathways of differentially expressed genes (DEGs), protein-protein interaction network, the filtering of hub genes, gene co-expression and the pathogenesis and prognosis were revealed by bioinformatics analysis. The correlation between hub gene expression and patient survival was validated by Kaplan-Meier. The effects of silent DNA replication and sister chromatid cohesion 1 (siDSCC1) combined with Lipitor and aspirin on DSCC1 expression, viability, invasion and migration of PCa cells were detected by qRT-PCR, Wound healing and transwell assays.

RESULTS

157 overlapped DEGs involved in FoxO, PI3K-Akt and p53 signaling pathways were identified. Ten hub genes (NEIL3, CDC7, DSCC1, CDC25C, PRIM1, MCM10, FBXO5, DTL, SERPINE1, EXO1) were verified to be correlated with the pathology and prognosis of PCa. DSCC1 silencing not only inhibited the viability, migration and invasion of PCa cells, but also strengthened the suppressing effects of Lipitor and aspirin alone or in combination on PCa cells.

CONCLUSION

The enrichment pathways and targets of Lipitor combined with aspirin in PCa are discovered, and DSCC1 silencing can potentiate the effect of Lipitor combined with aspirin in the treatment of PCa.

摘要

目的

我们之前的研究已经证实，阿司匹林联合立普妥可抑制前列腺癌（PCa）的发展，但需要全面阐述其机制。本研究旨在筛选出联合治疗的关键基因，并探讨其与 PCa 发病机制和预后的关系。

方法

采用 RNA 测序（RNA-seq）定量检测基因表达。通过生物信息学分析揭示差异表达基因（DEGs）的改变生物学功能、途径、蛋白质-蛋白质相互作用网络、关键基因的筛选、基因共表达以及发病机制和预后。通过 Kaplan-Meier 验证关键基因表达与患者生存的相关性。通过 qRT-PCR、划痕愈合和 Transwell 实验检测沉默 DNA 复制和姐妹染色单体黏合 1（siDSCC1）联合立普妥和阿司匹林对 PCa 细胞中 DSCC1 表达、活力、侵袭和迁移的影响。

结果

鉴定出 157 个涉及 FoxO、PI3K-Akt 和 p53 信号通路的重叠 DEGs。验证了 10 个关键基因（NEIL3、CDC7、DSCC1、CDC25C、PRIM1、MCM10、FBXO5、DTL、SERPINE1、EXO1）与 PCa 的病理学和预后相关。DSCC1 沉默不仅抑制了 PCa 细胞的活力、迁移和侵袭，而且还增强了立普妥和阿司匹林单独或联合应用对 PCa 细胞的抑制作用。