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Oncogenes associated with drug resistance in ovarian cancer

  • Review – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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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Abbreviations

ACTN4:

Actinin, alpha 4

AKT1:

v-akt murine thymoma viral oncogene homolog 1

AKT2:

v-akt murine thymoma viral oncogene homolog 2

BAD:

BCL2-associated agonist of cell death

BAX:

BCL2-associated X protein

BCL2:

B-cell CLL/lymphoma 2

MIEN1:

Migration and invasion enhancer 1

CLU:

Clusterin

CUZD1:

CUB and zona pellucida-like domains 1

DAXX:

Death-domain-associated protein

EGFR:

Epidermal growth factor receptor

ERBB2:

v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2

FOS:

FBJ murine osteosarcoma viral oncogene homolog

JUN:

Jun proto-oncogene

IKBKE:

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon

KRAS:

Kirsten rat sarcoma viral oncogene homolog

MAPK1:

Mitogen-activated protein kinase 1

MET:

Met proto-oncogene

MYC:

v-myc avian myelocytomatosis viral oncogene homolog

NFKB1:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

NINL:

Ninein-like

NOTCH3:

Notch 3

P53:

Tumor protein p53

PIK3CA:

Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, also know as PI3K

RSF1:

Remodeling and spacing factor 1

SRC:

v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog

STAT3:

Signal transducer and activator of transcription 3

URI:

URI1, prefoldin-like chaperone

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Acknowledgments

The study was supported by the National Natural Science Foundation of China (Grant No. 81302283) and China Postdoctoral Science Foundation (No. 2014M552535XB and No. 2014M552291).

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The authors confirm that they have no competing interests.

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Authors and Affiliations

  1. Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People’s Republic of China

    Xia Liu, Yi Lu & Jian Zhang

  2. Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Affiliated to Capital Medical University, Chaoyang District, Beijing, 100020, China

    Yutao Gao

  3. Medical Scientific Research Centre, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People’s Republic of China

    Li Li & Fuqiang Yin

  4. Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, 22 Shuangyong Road, Nanning, 530021 Guangxi, People’s Republic of China

    Li Li & Fuqiang Yin

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  1. Xia Liu
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  2. Yutao Gao
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  3. Yi Lu
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  4. Jian Zhang
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Correspondence to Fuqiang Yin.

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Liu, X., Gao, Y., Lu, Y. et al. Oncogenes associated with drug resistance in ovarian cancer. J Cancer Res Clin Oncol 141, 381–395 (2015). https://doi.org/10.1007/s00432-014-1765-5

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