Liu Xia, Gao Yutao, Lu Yi, Zhang Jian, Li Li, Yin Fuqiang
Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
J Cancer Res Clin Oncol. 2015 Mar;141(3):381-95. doi: 10.1007/s00432-014-1765-5. Epub 2014 Jul 6.
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.
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.
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.
癌基因在癌症发展中起关键作用，其表达紊乱与耐药性有关。然而，此前尚未有关于癌基因对卵巢癌耐药性贡献的综述报道。本研究旨在回顾卵巢癌中与耐药性相关的癌基因，并精确确定它们之间的关系。
总结现有文献中与卵巢癌耐药性相关的癌基因，并进行全面的生物信息学分析，包括通路富集、生物学过程注释、蛋白质/基因相互作用和微小RNA-信使核糖核酸相互作用分析。
整合并进一步分析了总共25个导致卵巢癌耐药的癌基因。基于先前发表的论文，绘制了一条癌基因介导的耐药通路，该通路解释了其中21个癌基因在耐药性中的关联。确定了v-akt小鼠胸腺瘤病毒癌基因（AKT）和B细胞淋巴瘤/白血病2相关X蛋白（BAX）相对于许多其他癌基因的下游位置，表明这两个基因可能起核心作用，且AKT和BAX介导的信号通路是癌基因参与卵巢癌耐药性的主要途径。此外，生物学过程注释表明，凋亡（细胞死亡）和磷酸化（磷酸盐代谢过程）可能是癌基因导致卵巢癌耐药的两条主要生物学途径。另外，基于对微小RNA-信使核糖核酸相互作用的综合分析，鉴定出11种微小RNA靶向25个癌基因中的至少7个，表明这些微小RNA可能是这25个癌基因的重要调节因子。总体而言，通过整合和进一步分析这些癌基因的现有数据，本研究有助于增进我们对其表达导致卵巢癌耐药机制的理解。
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