Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes

Wang,Huali; Yu,Yunhai; Chen,Chen; Wang,Qian; Huang,Taisheng; Hong,Fangzhen; Zhu,Lin

doi:10.3892/mmr.2015.3745

Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes

Authors:
- Huali Wang
- Yunhai Yu
- Chen Chen
- Qian Wang
- Taisheng Huang
- Fangzhen Hong
- Lin Zhu
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Affiliations: Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3745
Pages: 2503-2510
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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