Zhu Xingmei, Yang Jiani, Zhang Enhu, Qiao Wei, Li Xuejun
Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Oct 30;39(10):1141-1148. doi: 10.12122/j.issn.1673-4254.2019.10.02.
To explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis.
Drug Bank 5.1.3 was searched to identify direct protein targets (DPTs) of aspirin, and the protein-protein interaction (PPI) network of the DPTs was constructed online using STRING and the signaling pathways involved were identified. The genetic alterations of 6 DPTs associated with human breast cancer was analyzed and visualized by cBio Portal and OncoPrint, respectively. The transcriptomic data of breast cancer and normal tissues were downloaded from TCGA database, and the overexpressed genes were analyzed by DECenter. The intersection between the genes associated with the DPTs obtained by STRING analysis and the differentially over-expressed genes in TCGA was determined to confirm the candidate DPTs as a potential target of aspirin, and GO functional enrichment analysis was performed using Gene Ontology. The potential targets of aspirin against the proliferation of human breast cancer cells were verified by Western blotting.
Eleven DPTs of aspirin were identified. KEGG pathway enrichment indicated that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2 and TP53) were associated with the occurrence and development of cancer. A total of 10 220 differentially expressed genes were identified from the TCGA database, and among them 4 genes (, , , ) were found to be the potential targets for aspirin. These genes were involved mostly in the regulation of cell cycle and cell division. Western blotting showed that aspirin could down-regulate the expression levels of several pivotal proteins that regulated cell cycle and cell division, including , , and .
, , and may be potential targets for aspirin to inhibit the proliferation of human breast cancer cells, by affecting the progress of cell cycle and cell division.
通过生物信息学分析探讨阿司匹林抑制人乳腺癌细胞增殖的分子机制。
检索Drug Bank 5.1.3以鉴定阿司匹林的直接蛋白质靶点（DPT），使用STRING在线构建DPT的蛋白质-蛋白质相互作用（PPI）网络并鉴定其中涉及的信号通路。分别通过cBio Portal和OncoPrint分析与人类乳腺癌相关的6个DPT的基因改变并进行可视化。从TCGA数据库下载乳腺癌和正常组织的转录组数据，通过DECenter分析过表达基因。确定STRING分析获得的与DPT相关的基因与TCGA中差异过表达基因的交集，以确认候选DPT作为阿司匹林的潜在靶点，并使用基因本体进行GO功能富集分析。通过蛋白质印迹法验证阿司匹林针对人乳腺癌细胞增殖的潜在靶点。
鉴定出阿司匹林的11个DPT。KEGG通路富集表明6个基因（EDNRA、IKBKB、NFKB2、NFKBIA、PTGS2和TP53）与癌症的发生和发展相关。从TCGA数据库中共鉴定出10220个差异表达基因，其中4个基因（此处原文缺失具体基因名）被发现是阿司匹林的潜在靶点。这些基因主要参与细胞周期和细胞分裂的调控。蛋白质印迹法显示阿司匹林可下调几种调节细胞周期和细胞分裂的关键蛋白的表达水平，包括（此处原文缺失具体蛋白名）。
（此处原文缺失具体基因名）可能是阿司匹林抑制人乳腺癌细胞增殖的潜在靶点，其通过影响细胞周期和细胞分裂进程发挥作用。
