title: MiR-146b-5p promotes metastasis and induces epithelial-mesenchymal transition in thyroid cancer by targeting ZNRF3.
abstract: OBJECTIVE
  Micro-RNA (miR)-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and associated with extrathyroidal invasion and advanced tumor stage. In the present study, we showed that miR-146b-5p is upregulated in PTC with lymph node metastasis.
  
  
  METHODS
  A computational search and luciferase assay identified zinc RING finger 3 (ZNRF3), a negative regulator of Wnt/β-catenin signaling, as a direct target of miR-146b-5p in PTC.
  
  
  RESULTS
  MiR-146b-5p promoted migration and invasiveness and induced epithelial-mesenchymal transition (EMT) of PTC cells, whereas ZNRF3 overexpression reversed this effect. MiR-146b-5p increased the cell surface levels of the Wnt receptors Frizzled-6 and LRP6 and enhanced Wnt/β-catenin signaling by downregulating ZNRF3, whereas an inhibitor of Wnt/β-catenin suppressed the effect of miR-146b-5p on migration, invasiveness and EMT of PTC cells.
  
  
  CONCLUSIONS
  These results indicate that miR-146b-5p induces EMT and may promote PTC metastasis through the regulation of Wnt/β-catenin signaling, and suggest novel potential therapeutic targets for the treatment of PTC.
authors.affiliation: Center of Thyroid and Parathyroid, Department of General Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University of Medicine, Shanghai, China.
authors.forename: Xianzhao
authors.initials: X
authors.lastname: Deng
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Xiao
authors.forename: Jie
authors.initials: J
authors.lastname: Kang
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Youben
authors.initials: Y
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051157:Frizzled Receptors / Q000378:metabolism; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D016415:Sequence Alignment; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C484687:FZD6 protein, human; D051157:Frizzled Receptors; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D044767:Ubiquitin-Protein Ligases; C572950:ZNRF3 protein, human