Abstract
Context: Quercetin exerts antiproliferative effects on gastric cancer. However, its mechanisms of action on gastric cancer have not been comprehensively revealed.Objective: We investigated the mechanisms of action of quercetin against gastric cancer cells.Materials and methods: Human NCI-N87 gastric cancer cells were treated with 15 μM quercetin or dimethyl sulfoxide (as a control) for 48 h. DNA isolated from cells was sequenced on a HiSeq 2500, and the data were used to identify differentially expressed genes (DEGs) between groups. Then, enrichment analyses were performed for DEGs and a protein–protein interaction (PPI) network was constructed. Finally, the transcription factors (TFs)-DEGs regulatory network was visualized by Cytoscape software.Results: A total of 121 DEGs were identified in the quercetin group. In the PPI network, Fos proto-oncogene (FOS, degree = 12), aryl hydrocarbon receptor (AHR, degree = 12), Jun proto-oncogene (JUN, degree = 11), and cytochrome P450 family 1 subfamily A member 1 (CYP1A1, degree = 11) with higher degrees highly interconnected with other proteins. Of the 5 TF-DEGs, early growth response 1 (EGR1), FOS like 1 (FOSL1), FOS, and JUN were upregulated, while AHR was downregulated. Moreover, FOSL1, JUN, and Wnt family member 7B (WNT7B) were enriched in the Wnt signaling pathway.Discussion and conclusions: CYP1A1 highly interconnected with AHR in the PPI network. Therefore, FOS, AHR, JUN, CYP1A1, EGR1, FOSL1, and WNT7B might be targets of quercetin in gastric cancer.
Highlights
IntroductionGastric/stomach cancer is a type of cancer that originates from the lining of the stomach (Piazuelo and Correa 2013)
Gastric cancer accounts for 8.5% of all cancer cases in men, making it the fourth most common cancer in men in 2012 (Lozano et al 2012)
Upregulated genes were mainly enriched within the apical plasma membrane (CC, P 1⁄4 8.49E-03) in response to cAMP
Summary
Gastric/stomach cancer is a type of cancer that originates from the lining of the stomach (Piazuelo and Correa 2013). The major causes of gastric cancer are Helicobacter pylori infection, smoking, and dietary and genetic factors (Gonzalez et al 2013; Yang et al 2014). Gastric cancer is more common in men (Jemal et al 2015), suggesting that estrogen in women may confer protection from the disease (Jian et al 2014). Gastric cancer accounts for 8.5% of all cancer cases in men, making it the fourth most common cancer in men in 2012 (Lozano et al 2012). In 2012, there were 952,000 newly diagnosed cases of gastric cancer, and it was the fifth most common cancer globally (Peto et al 2014). Investigating the pathological mechanisms of gastric cancer is of great significance
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