Dataset Information

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

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.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC6171422 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

Zeng Yun Y Shen Zhengjie Z Gu Wenzhe W Wu Mianhua M

Pharmaceutical biology 20181201 1

<h4>Context</h4>Quercetin exerts antiproliferative effects on gastric cancer. However, its mechanisms of action on gastric cancer have not been comprehensively revealed.<h4>Objective</h4>We investigated the mechanisms of action of quercetin against gastric cancer cells.<h4>Materials and methods</h4>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 ide ...[more]

PMID: 30266078

Similar Datasets

Project description:For optimum radioimmunotherapy (RIT), deep penetration and uniform distribution into the tumor core is important. The solid tumor microenvironment, consisting of a highly fibrotic or desmoplastic tumor, abnormal tumor vasculature, high fluid pressure, and the absence of fluid lymphatics, limits the distribution of monoclonal antibodies mAbs to the tumor core. To investigate the optimal rationale for therapeutic mAbs administration and the microdistribution of mAbs, single and serial fractional dosage regimens of Cu-64-trastuzumab (TRZ) with paclitaxel were evaluated. Groups of nude mice were inoculated with gastric cancer cell line NCI-N87 tumor cells. When the tumor size reached 200 ± 20 mm3, the mice were divided into two groups for injection of Alexa-647-TRZ. One group (n = 5) was injected with 15 mg/kg in a single dose (SD), and the other group (n = 5) with two doses of 7.5 mg/kg (fractionated dose (FD)). In both cases, the injections were done intravenously in combination with intraperitoneal paclitaxel either as a SD of 70 mg/kg or fractionated into two doses of 40 and 30 mg/kg. Tumors were harvested, flash frozen, and sectioned (8 µm) five days after Alexa-647-TRZ injection. Rhodamine lectin (rhodamine-labeled Ricinus communis agglutinin I, 1 mg in 0.2 mL of phosphate-buffered saline (PBS)) was intravenously injected to delineate the functional vessel for a wait time of 5 min before animal euthanization. Microscopic images were acquired with an IN Cell Analyzer. The amount of TRZ that penetrated the tumor surface and the tumor vessel was calculated by area under the curve (AUC) analysis. For RIT efficacy (n = 21), Cu-64-TRZ was injected following the same dose schedule to observe tumor volume and survival ratio for 30 days. The SD and FD regimens of Alexa-647-TRZ were observed to have no significant difference in penetration of mAbs from the tumor edge and vessel, nor was the total accumulation across the whole tumor tissue significantly different. Additionally, the SD and FD regimens of Cu-64-TRZ were not proven to be significantly efficacious. Our study reveals that SD and FD in a treatment design with Cu-64-TRZ and paclitaxel shows no significant difference in therapeutic efficacy on tumor growth inhibition in vivo in mice bearing human gastric cancer xenografts overexpressing HER2 antigen.

Project description:BackgroundCurrently, there are no efficient therapies for Alzheimer's disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients' frontal cortex, current study aims to identify the potential mechanisms of quercetin's pharmacological targets.Materials and methodsThe pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.ResultsIn the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.ConclusionThe role of quercetin in AD appears to be multifaceted, and it can affect patients' frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.

Dataset Information

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

Context

Objective

Materials and methods

Results

Discussion and conclusions

Publications

Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets