Xu Shaohua, Xu Peizhen, Wu Wei, Ou Yangjun, Xu Juan, Zhang Guanghua, Li Jinping, Xu Guofeng
Department of Biomedical Science, Mercer University School of Medicine, Savanna, GA 31410, USA; Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Changzhou 213000, China.
Curr Pharm Des. 2014;20(11):1888-95. doi: 10.2174/13816128113199990523.
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic malignancies. Despite great efforts to improve early detection and optimize chemotherapeutic regimens, the 5-year survival rate is only 30% for patients presenting with late-stage ovarian cancer. The high mortality of this disease is due to late diagnosis in over 70% of ovarian cancer cases. A class of small noncoding RNAs, or microRNAs, was found to regulate gene expression at the post-transcriptional level. Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues. However, further stratification of the subject indicated that the expression levels of miR-200a were significantly downregulated in late-stage (FIGO III+V) and grade 3 groups compared with early stage (FIGO I+II) and grade 1 to 2 groups. Similarly, relatively low levels of miR-200a were observed in the lymph compared to the node-negative group. E-cadherin expression was found to be absent in normal ovarian tissue and was frequently expressed in benign epithelial ovarian cysts, with absence or low levels observed in late-stage ovarian cancers. There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer.
上皮性卵巢癌（EOC）是妇科恶性肿瘤中导致死亡的主要原因。尽管在改善早期检测和优化化疗方案方面付出了巨大努力，但晚期卵巢癌患者的5年生存率仅为30%。这种疾病的高死亡率归因于超过70%的卵巢癌病例诊断较晚。一类小的非编码RNA，即微小RNA，被发现可在转录后水平调节基因表达。部分（而非全部）数据表明，miR-200家族在多种恶性肿瘤中表达失调。在本研究中，我们证明与良性上皮性卵巢囊肿和正常卵巢组织相比，miR-200a和E-钙黏蛋白在EOC中显著上调。然而，对研究对象的进一步分层显示，与早期（FIGO I+II）和1至2级组相比，miR-200a的表达水平在晚期（FIGO III+V）和3级组中显著下调。同样，与无淋巴结转移组相比，在有淋巴结转移的病例中观察到相对较低水平的miR-200a。E-钙黏蛋白在正常卵巢组织中未表达，在良性上皮性卵巢囊肿中经常表达，而在晚期卵巢癌中表达缺失或水平较低。在EOC中，miR-200a与E-钙黏蛋白之间存在显著正相关。这种双相表达模式表明，miR-200a水平可能作为EOC早期检测的新型生物标志物，并且miR-200a和E-钙黏蛋白是开发抗卵巢癌新治疗模式的候选靶点。
