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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
  • View Affiliations / Copyright

    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
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2503-2510
    |
    Published online on: May 7, 2015
       https://doi.org/10.3892/mmr.2015.3745
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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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1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer. J Clin. 60:277–300. 2010. View Article : Google Scholar

2 

Ries L, Melbert D, Krapcho M, et al: SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute; pp. 1975–2005. 2008

3 

McGuire WP III and Markman M: Primary ovarian cancer chemotherapy: current standards of care. Br J Cancer. 89:S3–S8. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Agarwal R and Kaye SB: Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 3:502–516. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Crul M, Van Waardenburg R, Beijnen J and Schellens J: DNA-based drug interactions of cis platin. Cancer Treat Rev. 28:291–303. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C and Pérez JM: Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem. 7:3–18. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Rabik CA and Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 33:9–23. 2007. View Article : Google Scholar :

8 

Sedletska Y, Giraud-Panis MJ and Malinge JM: Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells: importance of apoptotic pathways. Curr Med Chem Anticancer Agents. 5:251–265. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Mandic A, Hansson J, Linder S and Shoshan MC: Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic signaling. J Biol Chem. 278:9100–9106. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Stewart DJ: Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 63:12–31. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Kelland L: The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 7:573–584. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Galluzzi L, Senovilla L, Vitale I, et al: Molecular mechanisms of cisplatin resistance. Oncogene. 31:1869–1883. 2012. View Article : Google Scholar

13 

Lee S, Choi EJ, Jin C and Kim DH: Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 97:26–34. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Yang X, Fraser M, Moll UM, Basak A and Tsang BK: Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer Res. 66:3126–3136. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Li M, Balch C, Montgomery JS, et al: Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer. BMC Med Genomics. 2:342009. View Article : Google Scholar : PubMed/NCBI

16 

Team RC: R:A language and environment for statistical computing. R foundation for Statistical Computing; 2005

17 

Irizarry RA, Hobbs B, Collin F, et al: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Smyth GK: Limma: Linear models for microarray data. Bioinformatics and computational biology solutions using R and Bioconductor Springer. pp. 397–420. 2005

19 

Sherman BT, Huang da W, Tan Q, et al: DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics. 8:4262007. View Article : Google Scholar : PubMed/NCBI

20 

Franceschini A, Szklarczyk D, Frankild S, et al: STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41:D808–D815. 2013. View Article : Google Scholar :

21 

Smoot ME, Ono K, Ruscheinski J, Wang PL and Ideker T: Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics. 27:431–432. 2011. View Article : Google Scholar :

22 

Nepusz T, Yu H and Paccanaro A: Detecting overlapping protein complexes in protein-protein interaction networks. Nat Methods. 9:471–472. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Rizzo S, Hersey JM, Mellor P, et al: Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther. 10:325–335. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Hu S, Yu L, Li Z, et al: Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo. Cancer Biol Ther. 10:788–795. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Bragado P, Armesilla A, Silva A and Porras A: Apoptosis by cisplatin requires p53 mediated p38α MAPK activation through ROS generation. Apoptosis. 12:1733–1742. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Qin LF and Ng IO: Induction of apoptosis by cisplatin and its effect on cell cycle-related proteins and cell cycle changes in hepatoma cells. Cancer Lett. 175:27–38. 2002. View Article : Google Scholar

27 

Tsang DP and Cheng AS: Epigenetic regulation of signaling pathways in cancer: Role of the histone methyltransferase EZH2. J Gastroenterol Hepatol. 26:19–27. 2011. View Article : Google Scholar

28 

Hu S, Yu L, Li Z, et al: Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo. Cancer Biol Ther. 10:788–795. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Rizzo S, Hersey JM, Mellor P, et al: Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther. 10:325–335. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Lv Y, Yuan C, Xiao X, et al: The expression and significance of the enhancer of zeste homolog 2 in lung adenocarcinoma. Oncol Rep. 28:147–154. 2012.PubMed/NCBI

31 

Caldon CE, Sergio CM, Kang J, et al: Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells. Mol Cancer Ther. 11:1488–1499. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Zheng L, Zhao Y, Feng H and Liu Y: Endocrine resistance in breast cancer. Climacteric. 1–7. 2013.

33 

Tu SH, Ho CT, Liu MF, et al: Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression. Food Chem. 141:1553–1561. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Gao T, Han Y, Yu L, Ao S, Li Z and Ji J: CCNA2 is a prognostic biomarker for ER+Breast cancer and tamoxifen resistance. Plos One. 9:e917712014. View Article : Google Scholar

35 

Gao K, Lockwood WW, Li J, Lam W and Li G: Genomic analyses identify gene candidates for acquired irinotecan resistance in melanoma cells. Int J Oncol. 32:1343–1349. 2008.PubMed/NCBI

36 

Klebig C, Korinth D and Meraldi P: Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 185:841–858. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Jeganathan K, Malureanu L, Baker DJ, Abraham SC and van Deursen JM: Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. J Cell Biol. 179:255–267. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Pinto M, Vieira J, Ribeiro FR, et al: Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas. Cell Oncol. 30:389–395. 2008.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang H, Yu Y, Chen C, Wang Q, Huang T, Hong F and Zhu L: Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes. Mol Med Rep 12: 2503-2510, 2015.
APA
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., & Zhu, L. (2015). Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes. Molecular Medicine Reports, 12, 2503-2510. https://doi.org/10.3892/mmr.2015.3745
MLA
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., Zhu, L."Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes". Molecular Medicine Reports 12.2 (2015): 2503-2510.
Chicago
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., Zhu, L."Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes". Molecular Medicine Reports 12, no. 2 (2015): 2503-2510. https://doi.org/10.3892/mmr.2015.3745
Copy and paste a formatted citation
x
Spandidos Publications style
Wang H, Yu Y, Chen C, Wang Q, Huang T, Hong F and Zhu L: Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes. Mol Med Rep 12: 2503-2510, 2015.
APA
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., & Zhu, L. (2015). Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes. Molecular Medicine Reports, 12, 2503-2510. https://doi.org/10.3892/mmr.2015.3745
MLA
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., Zhu, L."Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes". Molecular Medicine Reports 12.2 (2015): 2503-2510.
Chicago
Wang, H., Yu, Y., Chen, C., Wang, Q., Huang, T., Hong, F., Zhu, L."Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes". Molecular Medicine Reports 12, no. 2 (2015): 2503-2510. https://doi.org/10.3892/mmr.2015.3745
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