title: Celecoxib exhibits an anti-gastric cancer effect by targeting focal adhesion and leukocyte transendothelial migration-associated genes.
abstract: Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database. Two groups of differentially expressed genes (DEGs) were identified using limma package in R language. The criterion for GSE56807 was a false discovery rate of <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets were screened out. Subsequently, pathway enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery software (P<0.1; gene count ≥2). In addition, the protein-protein interactions (PPIs) among the overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins, Biomolecular Interaction Network Database and Human Protein Reference Database. Finally, a PPI network was visualized using Cytoscape software. A total of 137 overlapped DEGs were obtained, and DEGs with opposite regulation directions in the two datasets were significantly enriched in focal adhesion and leukocyte transendothelial migration. Subsequently, a PPI network of overlapped DEGs was constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich protein 1 (CSRP1), thrombospondin 1 (THBS1), myosin light chain 9 (MYL9), filamin A (FLNA), actinin alpha 1 (ACTN1), vinculin (VCL), laminin subunit gamma 2 (LAMC2) and claudin 1 (CLDN1)] were upregulated in GC tissues and downregulated in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects by suppressing the expression ofCSRP1,THBS1,MYL9,FLNA,ACTN1,VCL,LAMC2andCLDN1, and inhibiting leukocyte transendothelial migration and focal adhesion. However, relevant experiments are required to confirm the conclusion of the present study.
authors.affiliation: Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Jin
authors.affiliation: Department of Laboratory, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Wang
keywords: anticancer mechanism; celecoxib; gastric cancer; pathway enrichment analysis; protein-protein interaction