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Involvement of enhancer of zeste homolog 2 in cisplatinresistance in ovarian cancer cells by interacting with several genes

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In the present study, gene expression profiles of cisplatinsensitive ovarian cancer (OC) cells were compared with those of cisplatinresistant 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 cisplatinsensitive OC cells and five biological replicates of cisplatinresistant OC cells. Differentially expressed genes (DEGs) were screened using the limma package in R, based on the cutoff 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 proteinprotein interaction (PPI) network was constructed for the DEGs using STRING, and subnetworks were analyzed by Clustering with Overlapping Neighborhood Expansion. A total of 556 DEGs were identified in the cisplatinsensitive OC cells, of which 246 were upregulated and 310 were downregulated. Functional enrichment analysis revealed metabolismassociated 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 cisplatinresistance of OC were revealed, particularly EZH2. These findings assist in the development of therapy for OC.
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Document Type: Research Article

Affiliations: 1: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China 2: Department of Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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