title: Upregulation of kazrin F by miR-186 suppresses apoptosis but promotes epithelial-mesenchymal transition to contribute to malignancy in human cervical cancer cells.
abstract: OBJECTIVE
  Previous studies have identified that kazrin is a constituent of desmosome and influences intercellular adhesion, growing development and morphology. We previously cloned another new isoform, kazrin F and found that it has anti-apoptotic effects on human glioma cell line. To further explore whether kazrin F is involved in tumorigenesis, we investigated its expression and role in cervical cancer (CC) cells.
  
  
  METHODS
  The role of kazrin F and miR-186 in CC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell, and apoptosis assays. Using enhanced green fluorescent protein (EGFP) reporter assays, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, we identified kazrin F post-transcriptional regulation by miR-186.
  
  
  RESULTS
  We demonstrate that kazrin F is highly expressed in CC tissues compared with the adjacent noncancerous tissues and promotes cell proliferation, colony formation, migration and invasion in HeLa and C33A cells by suppressing apoptosis and facilitating epithelial-to-mesenchymal transition (EMT). Furthermore, miR-186 was confirmed as a regulator of kazrin F dysregulation. An EGFP reporter assay proved that miR-186 directly targets the 3'-untranslated region (3'UTR) of kazrin F and downregulates its expression, and miR-186 expression showed an inverse correlation with kazrin F levels in CC tissues. In addition, overexpression of miR-186 suppressed the malignant behaviors of CC cells. The ectopic expression of kazrin F rescued the inhibitory effects of miR-186.
  
  
  CONCLUSIONS
  Our findings indicate that the upregulation of kazrin F due to downregulated miR-186 levels contributes to malignancy, and highlight the significance of kazrin F in CC tumorigenesis.
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Tianjin Life Science Research Center and Department of Pathogen, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
keywords: EMT; Kazrin F; apoptosis; cervical cancer; miR-186