Wang Yu, Yan Shi, Liu Xiaolin, Zhang Wenjing, Li Yingwei, Dong Ruifen, Zhang Qing, Yang Qifeng, Yuan Cunzhong, Shen Keng, Kong Beihua
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
Department of Breast Surgery, Qilu Hospital, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2014 Apr;31(4):1905-10. doi: 10.3892/or.2014.3046. Epub 2014 Feb 24.
Ovarian cancer, particularly high-grade serous ovarian carcinoma (HG-SOC), is still the main cause of death among gynecological malignancies. However, the molecular mechanisms related to its malignant biological behavior are still unclear. Recent studies indicate that microRNAs (miRNAs) play an important role in tumor metastasis. Here, we report that miR-1236-3p expression was downregulated in HG-SOC when compared to that in normal fallopian tube tissue. Manipulation of miR-1236-3p significantly influenced the morphology, migration and invasion of ovarian cancer cell lines (A2780 and SKOV3). With dual-luciferase reporter assay, we demonstrated that miR‑1236-3p binds to the 3'UTR of zinc-finger E-box binding homeobox 1 (ZEB1) mRNA, and functions as a negative regulator of ZEB1. Furthermore, we revealed that manipulation of miR-1236-3p modulates ZEB1 expression and influences expression of its downstream genes E-cadherin and N-cadherin at both the mRNA and protein levels. We also found an inverse relationship between miR‑1236-3p and ZEB1 expression in the HG-SOC tissue samples. Taken together, our results indicate that miR-1236-3p regulates ovarian cancer metastasis by directly targeting ZEB1, and it may play an important role in the diagnosis and treatment of ovarian cancer.
卵巢癌，尤其是高级别浆液性卵巢癌（HG-SOC），仍然是妇科恶性肿瘤死亡的主要原因。然而，与其恶性生物学行为相关的分子机制仍不清楚。最近的研究表明，微小RNA（miRNA）在肿瘤转移中起重要作用。在此，我们报告称，与正常输卵管组织相比，HG-SOC中miR-1236-3p的表达下调。对miR-1236-3p的调控显著影响卵巢癌细胞系（A2780和SKOV3）的形态、迁移和侵袭。通过双荧光素酶报告基因检测，我们证明miR-1236-3p与锌指E盒结合同源框1（ZEB1）mRNA的3'非翻译区结合，并作为ZEB1的负调节因子发挥作用。此外，我们发现对miR-1236-3p的调控在mRNA和蛋白质水平上调节ZEB1的表达，并影响其下游基因E-钙黏蛋白和N-钙黏蛋白的表达。我们还在HG-SOC组织样本中发现了miR-1236-3p与ZEB1表达之间的负相关关系。综上所述，我们的结果表明，miR-1236-3p通过直接靶向ZEB1来调节卵巢癌转移，并且它可能在卵巢癌的诊断和治疗中发挥重要作用。
