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基于基因芯片表达谱的生物信息学分析鉴定了绿茶多酚表没食子儿茶素没食子酸酯通过调节黏着斑激酶信号通路对乳腺癌细胞增殖和凋亡的作用机制。

Bioinformatics analysis of microarray profiling identifies the mechanism of focal adhesion kinase signalling pathway in proliferation and apoptosis of breast cancer cells modulated by green tea polyphenol epigallocatechin 3-gallate.

机构信息

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Department of Dialysis Room of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

出版信息

J Pharm Pharmacol. 2018 Dec;70(12):1606-1618. doi: 10.1111/jphp.13010. Epub 2018 Sep 5.

Abstract

OBJECTIVES

This study aimed to investigate potential gene and signal pathway associated with tumour progression.

METHODS

Related microarray data set of breast cancer was obtained from Gene Expression Omnibus database, and differential-expressed genes (DEGs) between two control samples and two treated samples were analysed using statistical software R. We collected 50 epigallocatechin-3-gallate(EGCG)-related genes and 119 breast cancer-related genes to create a knowledge base for following pathway analysis.

KEY FINDINGS

A total of 502 mRNAs were identified as DEGs based on microarray analysis. Upregulated DEGs mainly enriched in nuclear nucleosome, cell adhesion, DNA packaging complex, Wnt-activated receptor activity, etc., while the downregulated DEGs significantly enriched in ncRNA processing, mitotic nuclear division, DNA helicase activity, etc. DEGs mostly enriched in gap junction, cell cycle, oxidative phosphorylation, focal adhesion, etc. EGCG suppressed FAK signalling pathway. Furthermore, EGCG could inhibit breast cancer cell proliferation and promote apoptosis by modulating CCND1.

CONCLUSIONS

Epigallocatechin 3-gallate might exert influence on breast cancer progression through inhibiting focal adhesion kinase (FAK) signalling pathway.

摘要

目的

本研究旨在探讨与肿瘤进展相关的潜在基因和信号通路。

方法

从基因表达综合数据库中获取乳腺癌相关的微阵列数据集,使用统计软件 R 分析两个对照样本和两个处理样本之间的差异表达基因(DEGs)。我们收集了 50 个表没食子儿茶素没食子酸酯(EGCG)相关基因和 119 个乳腺癌相关基因,以创建用于后续通路分析的知识库。

主要发现

基于微阵列分析,共鉴定出 502 个 mRNAs 为 DEGs。上调的 DEGs 主要富集在核小体、细胞黏附、DNA 包装复合物、Wnt 激活受体活性等,而下调的 DEGs 则显著富集在 ncRNA 加工、有丝分裂核分裂、DNA 解旋酶活性等。DEGs 主要富集在间隙连接、细胞周期、氧化磷酸化、黏着斑等通路中。EGCG 抑制 FAK 信号通路。此外,EGCG 可以通过调节 CCND1 来抑制乳腺癌细胞增殖并促进细胞凋亡。

结论

表没食子儿茶素没食子酸酯可能通过抑制黏着斑激酶(FAK)信号通路对乳腺癌的进展产生影响。

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