title: HIFs-MiR-33a-Twsit1 axis can regulate invasiveness of hepatocellular cancer cells.
abstract: In this study, we investigated whether miR-33a downregulation in HCC is a result of hypoxia-inducible factors (HIFs) overexpression. Then, we further studied the regulative effects of miR-33a on Twist1 and their regulation in HCC cell invasiveness.
  
  
  
  Human hepatocellular cancer (HCC) cell lines (HepG2 and BEL-7402) were transfected with miR-33a mimics, HIFs siRNA or Twist1 siRNA. MiR-33a level was measured using QRT-PCR. The binding between miR-33a and Twist1 3'UTR was verified using Western blot analysis and dual luciferase assay. E-cadherin and N-cadherin expression levels were detected by western blot analysis. Tumor cell invasion was assessed using transwell assay.
  
  
  
  MiR-33a downregulation in HCC cells is hypoxia-induced and is a result of HIFs upregulation. HIF-1α and HIF-2α suppression partly rescued miR-33a expression under hypoxia. Both HepG2 and BEL-7402 cells with miR-33a overexpression had significantly decreased E-cadherin expression and increased N-cadherin level. Transwell analysis confirmed that miR-33a overexpression significantly suppressed the tumor cell invasion capability. Twist1 is a direct target of miR-33a in HCC. HepG2 cells with Twist1 knockdown had significantly increased E-cadherin, decreased N-cadherin and suppressed invasion capability.
  
  
  
  MiR-33a downregulation in HCC cells is hypoxia-induced and is a result of HIFs upregulation. MiR-33a can modulate EMT and invasion of hepatocellular cancer cells at least partly via downregulating Twist1.
authors.affiliation: Department of Infectious Liver Diseases, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China. junliu80s@outlook.com.
authors.forename: X-F
authors.initials: XF
authors.lastname: Guo
authors.forename: A-Y
authors.initials: AY
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D015703:Antigens, CD; D015820:Cadherins; D006528:Carcinoma, Hepatocellular; D006801:Humans; D008113:Liver Neoplasms; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C550416:MIRN33a microRNA, human; D035683:MicroRNAs