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Review
. 2015 Mar;141(3):381-95.
doi: 10.1007/s00432-014-1765-5. Epub 2014 Jul 6.

Oncogenes associated with drug resistance in ovarian cancer

Xia Liu  1 , Yutao Gao, Yi Lu, Jian Zhang, Li Li, Fuqiang Yin
Affiliations
Review

Oncogenes associated with drug resistance in ovarian cancer

Xia Liu et al. J Cancer Res Clin Oncol. 2015 Mar.

Abstract

Purpose: Oncogenes play pivotal roles in the development of cancer, and disturbances in their expression have been implicated in drug resistance. However, an overview of the contribution of oncogenes to drug resistance in ovarian cancer has not previously been reported. This study aimed to review the drug resistance-related oncogenes in ovarian cancer and precisely determine their relationships.

Methods: The oncogenes associated with drug resistance in ovarian cancer from available papers were summarized, and a comprehensive bioinformatics analysis including pathway enrichment, biological processes annotation, protein/gene interaction and microRNA-mRNA interaction was performed.

Results: Total of 25 oncogenes contributing to drug resistance in ovarian cancer was integrated and further analyzed. An oncogene-mediated drug resistance pathway that explains the associations of 21 of these oncogenes in drug resistance was drafted on the basis of previously published papers. The downstream location of v-akt murine thymoma viral oncogene (AKT) and B-cell CLL/lymphoma 2-associated X protein (BAX) with respect to many other oncogenes was determined, indicating that the two genes may play a central role, and the AKT- and BAX-mediated signaling are the main pathways accounting for the involvement of oncogenes in drug resistance in ovarian cancer. Besides, the annotation of biological process indicated that the apoptosis (cell death) and phosphorylation (phosphate metabolic process) might be the two major biological routes through which oncogenes contribute to drug resistance in ovarian cancer. In addition, on the basis of the comprehensive analysis of microRNA-mRNA interactions, 11 microRNAs were identified to be targeted at least 7 of the 25 oncogenes, indicating that those microRNAs could be an important regulator of the 25 oncogenes. Collectively, by integrating and further analyzing the available data on these oncogenes, this study contributes to improving our understanding of the mechanisms by which their expression leads to drug resistance in this ovarian cancer.

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Conflict of interest statement

The authors confirm that they have no competing interests.

Figures

Fig. 1
Fig. 1
The distribution of the 14 oncogenes in three most highly annotated signaling pathways (ErbB, neurotrophin, and MAPK)
Fig. 2
Fig. 2
The oncogene-mediated drug resistance pathway drafted in accordance with previous studies of the 25 oncogenes contributing to drug resistance in ovarian cancer. The genes in blue are among the 25 oncogenes included in this study. The pathway covered all 25 oncogenes except CUZD1, DAXX, MYC, and NINL
Fig. 3
Fig. 3
The cohesive drug resistance pathway mediated by AKT, BAX, and several other oncogenes was generated according to the previous studies in ovarian cancer
Fig. 4
Fig. 4
The protein/gene interaction network of the 25 oncogenes, based on the GeneMania online tool. The protein/gene relationships are indicated in the network legend. Predicted interactions between the oncogenes were excluded
See this image and copyright information in PMC

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