miR-1236-3p represses the cell migration and invasion abilities by targeting ZEB1 in high-grade serous ovarian carcinoma
miR-1236-3p represses the cell migration and invasion abilities by targeting ZEB1 in high-grade serous ovarian carcinoma
复制标题
miR-1236-3p通过靶向ZEB1抑制高级别浆液性卵巢癌中的细胞迁移和侵袭能力
DOI：
10.3892/or.2014.3046
复制
发表时间：
2014-04-01
期刊：
影响因子：
4.2
通讯作者：
Kong, Beihua
中科院分区：
文献类型：
--
作者：
Wang, Yu;Yan, Shi;Kong, Beihua
卵巢癌，尤其是高级别浆液性卵巢癌(HG-SOC)，仍是妇科恶性肿瘤的主要死因。然而，与其恶性生物学行为相关的分子机制尚不清楚。最近的研究表明，microRNAs(MiRNAs)在肿瘤转移中起着重要作用。在此，我们报告与正常输卵管组织相比，miR-1236-3p在HG-SOC中的表达下调。MiR-1236-3p对卵巢癌细胞株(A2780和SKOV3)的形态、迁移和侵袭能力有显著影响。通过双荧光素酶报告实验，我们证明miR-1236-3p能与锌指E盒结合同源框1(ZEB1)的3‘非编码区结合，并对ZEB1起负调控作用。此外，我们还发现，miR-1236-3p的操作调控了ZEB1的表达，并在mRNA和蛋白水平上影响了其下游基因E-钙粘蛋白和N-钙粘蛋白的表达。我们还发现在HG-SOC组织中miR-1236-3p和ZEB1的表达呈负相关。综上所述，我们的结果表明miR-1236-3p通过直接靶向ZEB1来调控卵巢癌的转移，它可能在卵巢癌的诊断和治疗中发挥重要作用。
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.