title: Involvement of enhancer of zeste homolog 2 in cisplatin-resistance in ovarian cancer cells by interacting with several genes.
abstract: In the present study, gene expression profiles of cisplatin-sensitive ovarian cancer (OC) cells were compared with those of cisplatin-resistant OC cells to identify key genes and pathways contributing to cisplatin resistance in ovarian cancer cells. The GSE15372 gene expression data set was downloaded from Gene Expression Omnibus, and included five biological replicates of cisplatin-sensitive OC cells and five biological replicates of cisplatin-resistant OC cells. Differentially expressed genes (DEGs) were screened using the limma package in R, based on the cut-off values of P<0.05 and |log2 (fold change)|>1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology enrichment analysis were performed on the DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein-protein interaction (PPI) network was constructed for the DEGs using STRING, and sub-networks were analyzed by Clustering with Overlapping Neighborhood Expansion. A total of 556 DEGs were identified in the cisplatin-sensitive OC cells, of which 246 were upregulated and 310 were downregulated. Functional enrichment analysis revealed metabolism-associated pathways, DNA replication and cell cycle were significantly enriched in the downregulated genes, while cell growth and differentiation, response to stimulus, and apoptosis were significantly enriched in the upregulated genes. A PPI network, including 342 nodes was constructed for the DEGs and four subnetworks were extracted from the entire network. A total of 34 DEGs interacting with enhancer of zeste homolog 2 (EZH2) were identified, which were associated with DNA replication, pyrimidine metabolism and cell cycle. In conclusion, a number of key genes and pathways associated with the cisplatin-resistance of OC were revealed, particularly EZH2. These findings assist in the development of therapy for OC.
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Huali
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Hong
authors.affiliation: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D058977:Molecular Sequence Annotation; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D002945:Cisplatin