title: The role of miR-200a in vasculogenic mimicry and its clinical significance in ovarian cancer.
abstract: OBJECTIVE
  Vasculogenic mimicry (VM) indicates that aggressive cancer cells can form de novo vascular networks and provide a perfusion pathway for rapidly growing tumors. MiR-200a has been reported significantly deregulated in ovarian cancer. However, miR-200a regulation of VM and its clinical significance in ovarian cancer remain not elucidated.
  
  
  METHODS
  In this study, we identified the VM structure by CD34-PAS staining in ovarian cancer tissue. MiR-200a and protein expression was tested by quantitative RT-PCR and western blot. Bioinformatics prediction, luciferase assay and intervention experiments were employed to identify the target of miR-200a.
  
  
  RESULTS
  We certified the VM structure in ovarian cancer, and found that the VM positive rate was significantly associated with tumor grade, stage and metastasis. Further study showed that miR-200a expression levels were significantly lower in VM positive ovarian cancer. In addition, our results suggested that miR-200a inhibited VM by negatively regulated EphA2 expression. Consistently, the inverse correlation of miR-200a and EphA2 has also been found in ovarian cancer patients. Moreover, the expression of miR-200a/EphA2 was significantly associated with patient's clinicopathological parameter, such as tumor stage and metastases. Kaplan-Meier curves confirmed that the patients with low miR-200a expression and/or VM positive had a significantly shorter overall survival.
  
  
  CONCLUSIONS
  Our research demonstrates that VM, miR-200a and EphA2 play key roles in the progression and prognosis of ovarian cancer, and for the first time suggests that miR-200a inhibits VM by directly regulating EphA2. Therefore, we might have identified a genetic mechanism underlying the involvement of miR-200a in ovarian cancer VM.
authors: Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; Department of Pharmacy, Affiliated Wuxi Hospital for Maternal and Child Health Care of Nanjing Medical University, Wuxi 214002, China. Electronic address: qingminsun@gmail.com.
authors: Qingmin
authors: Q
authors: Sun
authors: Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
authors: Xi
authors: X
authors: Zou
authors: Department of Pharmacy, Affiliated Wuxi Hospital for Maternal and Child Health Care of Nanjing Medical University, Wuxi 214002, China.
authors: Ting
authors: T
authors: Zhang
authors: Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
authors: Jian
authors: J
authors: Shen
authors: Department of Pharmacy, Affiliated Wuxi Hospital for Maternal and Child Health Care of Nanjing Medical University, Wuxi 214002, China.
authors: Yongxiang
authors: Y
authors: Yin
authors: Department of Pharmacy, Affiliated Wuxi Hospital for Maternal and Child Health Care of Nanjing Medical University, Wuxi 214002, China. Electronic address: wxxjy89@163.com.
authors: Jingying
authors: J
authors: Xiang
mesh_terms: D020413:3' Untranslated Regions; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics*; D036104:Receptor, EphA2 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D018952:Antigens, CD34; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D036104:Receptor, EphA2
keywords: EphA2; Ovarian cancer; Vasculogenic mimicry; miR-200a