title: Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31.
abstract: OBJECTIVE
  This research aimed to examine the relationship between Dock1 and miR-31 and to determine the effect of miR-31 on the mesenchymal transition and invasiveness of glioma.
  
  
  METHODS
  Real-time PCR was used to measure the expression of miR-31 and other RNAs. The transfection was used to manipulate the expression levels of Dock1 and miR-31 in cancer cells. Western blot was used to detect the expression of Dock1 and other related proteins. Wound healing, Matrigel invasion and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-31 to the 3'-untranslated region of Dock1 was confirmed through luciferase assay and RNA immunoprecipitation. Methylation-specific PCR was performed to detect the methylation level of miR-31 in both glioma cell lines and tissues.
  
  
  RESULTS
  Dock1 can promote the IL8-induced chemotaxis and mesenchymal transition of glioma cells through the NF-κB/Snail signalling pathway. The protein levels of Dock1 in glioma cell lines and clinical specimens were negatively correlated with miR-31 expression, and Dock1 was directly targeted by miR-31. Animal experiments showed that Dock1 downregulation and miR-31 overexpression reduced glioma cell invasion. Investigation of the underlying molecular mechanism revealed that miR-31 downregulation was attributable to the hypermethylation of the promoter region of miR-31 in glioma cells.
  
  
  CONCLUSIONS
  Dock1 modulation by miR-31 plays an important function in glioma invasion both in vitro and in vivo. This study provides new insights into the invasion of glioma cells and might therefore contribute to the development of new antiglioma strategies.
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Baogang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Medicine Research Center, Weifang Medical University, Weifang, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Nursing, Weifang Medical University, Weifang, China.
authors.forename: Chonggao
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C099818:DOCK1 protein, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D020744:rac GTP-Binding Proteins
keywords: Dock1; mesenchymal transition; miR-31