Dept. of Medical Oncology, Josephine Nefkens Institute, Erasmus MC, 3015 GE Rotterdam, The Netherlands.
Int J Biochem Cell Biol. 2010 Aug;42(8):1282-90. doi: 10.1016/j.biocel.2010.01.014. Epub 2010 Jan 18.
Epithelial ovarian cancer is the most common cause of death from gynecological malignancies in the Western world. The overall 5-year survival is only 30% due to late diagnosis and development of resistance to chemotherapy. There is, therefore, a strong need for prognostic and predictive markers to help optimize and personalize treatment hence ameliorating the prognosis of ovarian cancer patients. Since 2006, an increasing number of studies have indicated an essential role for microRNAs in ovarian cancer tumorigenesis. In this review, we provide an overview of the microRNAs that have been associated with different aspects of ovarian cancer, such as tumor subtype, stage, histological grade, germline mutations in BRCA genes, prognosis and therapy resistance. We highlight the role of the let-7 and miR-200 families, two major microRNA families that are frequently dysregulated in ovarian cancer and have been associated with poor prognosis. Interestingly, both have been implicated in the regulation of the epithelial-to-mesenchymal transition, a cellular transition associated with tumor aggressiveness, tumor invasion and chemoresistance. Furthermore, we discuss several other microRNAs that have been associated with chemotherapy resistance, such as miR-214, miR-130a, miR-27a and miR-451. In the final section, we speculate on the possibilities of microRNA-based therapies and the use of microRNAs as diagnostic tools.
上皮性卵巢癌是西方世界妇科恶性肿瘤死亡的最主要原因。由于诊断较晚和对化疗产生耐药，总体 5 年生存率仅为 30%。因此，强烈需要预后和预测标志物来帮助优化和个体化治疗，从而改善卵巢癌患者的预后。自 2006 年以来，越来越多的研究表明 microRNAs 在卵巢癌肿瘤发生中具有重要作用。在这篇综述中，我们概述了与卵巢癌的不同方面相关的 microRNAs，例如肿瘤亚型、分期、组织学分级、BRCA 基因突变、预后和化疗耐药。我们强调了 let-7 和 miR-200 家族的作用，这两个主要的 microRNA 家族在卵巢癌中经常失调，并与不良预后相关。有趣的是，它们都与上皮-间充质转化的调节有关，上皮-间充质转化是与肿瘤侵袭性、肿瘤侵袭和化疗耐药相关的细胞转化。此外，我们还讨论了其他一些与化疗耐药相关的 microRNAs，如 miR-214、miR-130a、miR-27a 和 miR-451。在最后一节中，我们推测了基于 microRNA 的治疗的可能性和将 microRNAs 用作诊断工具的可能性。
