Xingmei Zhu1,2,3, Jiani Yang1,2,3, Enhu Zhang1,2, Wei Qiao4, Xuejun Li5. 1. Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China. 2. Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China. 3. Shaanxi Key Laboratory of Traditional Medicine Foundation and New Drug Research, Xianyang 712046, China. 4. Department of Gastroenterology, 521 Hospital of Norinco Group, Shaanxi, Xi'an, 710065, China. 5. School of Basic Medicine, Peking University Health Science Center, Beijing, 100191, China.
Abstract
OBJECTIVE: To explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis. METHODS: 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. RESULTS: 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 (CDC25C, TPX2, CDC20, PLK1) 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 CDC25C, TPX2, CDC20 and PLK1. CONCLUSIONS: CDC25C, TPX2, CDC20 and PLK1 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.
OBJECTIVE: To explore the molecular mechanism underlying the inhibitory effects of aspirin against humanbreast cancer cell proliferation through bioinformatics analysis. METHODS: 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 humanbreast 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 humanbreast cancer cells were verified by Western blotting. RESULTS: 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 (CDC25C, TPX2, CDC20, PLK1) 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 CDC25C, TPX2, CDC20 and PLK1. CONCLUSIONS:CDC25C, TPX2, CDC20 and PLK1 may be potential targets for aspirin to inhibit the proliferation of humanbreast cancer cells, by affecting the progress of cell cycle and cell division.
Entities:
Keywords:
aspirin; bioinformatics; cell cycle; cell division; human breast cancer
Authors: MohammadA Sabbaghi; Gabriel Gil-Gómez; Cristina Guardia; Sonia Servitja; Oriol Arpí; Sara García-Alonso; Silvia Menendez; Montserrat Arumi-Uria; Laia Serrano; Marta Salido; Aura Muntasell; Maria Martínez-García; Sandra Zazo; Cristina Chamizo; Paula González-Alonso; Juan Madoz-Gúrpide; Pilar Eroles; Joaquin Arribas; Ignasi Tusquets; Ana Lluch; Atanasio Pandiella; Federico Rojo; Ana Rovira; Joan Albanell Journal: Clin Cancer Res Date: 2017-08-18 Impact factor: 12.531
Authors: Jixia Li; Feng Zhu; Ronald A Lubet; Antonella De Luca; Clinton Grubbs; Marna E Ericson; Amelia D'Alessio; Nicola Normanno; Zigang Dong; Ann M Bode Journal: Mol Carcinog Date: 2011-11-15 Impact factor: 4.784
Authors: Danielle D Jandial; Lauren S Krill; Lixia Chen; Chunli Wu; Yu Ke; Jun Xie; Bang H Hoang; Xiaolin Zi Journal: Molecules Date: 2017-03-14 Impact factor: 4.411