title: MiR-32 functions as a tumor suppressor and directly targets EZH2 in human oral squamous cell carcinoma.
abstract: BACKGROUND
  MicroRNA-32 (miR-32) is dysregulated in certain human malignancies and correlates with tumor progression. However, its expression and function in oral squamous cell carcinoma (OSCC) remain unclear. Thus, the aim of this study was to explore the effects of miR-32 expression on OSCC tumorigenesis and development.
  
  
  METHODS
  Real-time quantitative PCR was applied to evaluate the expression level of miR-32 in OSCC cell lines and primary tumor tissues. The association of miR-32 expression with clinicopathological factors and prognosis was also analyzed. In vitro cell proliferation, apoptosis, invasion, and migration assays were executed to elucidate biological effects of miR-32. Western blotting and luciferase assays were performed to confirm the regulation of EZH2 by miR-32.
  
  
  RESULTS
  Down-regulation of miR-32 was found in OSCC tissues compared with corresponding noncancerous tissues (P<0.001). Decreased miR-32 expression was significantly associated with advanced T classifications, positive N classification, advanced TNM stage, and shorter overall survival (all P<0.05). Multivariate regression analysis corroborated that low-level expression of miR-32 was an independent unfavorable prognostic factor for OSCC patients. In vitro functional assays showed that overexpression of miR-32 reduced OSCC cell proliferation, migration, and invasion, and promoted cell apoptosis. In contrast, miR-32 knock-down resulted in an increase in cell growth and invasiveness. Finally, we identified EZH2 as the functional downstream target of miR-32 by directly targeting the 3'-UTR of EZH2.
  
  
  CONCLUSIONS
  These findings indicate that miR-32 may act as a tumor suppressor in OSCC and could serve as a novel therapeutic agent for miR-based therapy.
authors.affiliation: Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
authors.forename: Dafeng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
authors.forename: Xingqiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
authors.forename: Jin
authors.initials: J
authors.lastname: Xiao
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D015999:Multivariate Analysis; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014162:Transfection
chemical_list: C568529:MIRN32 microRNA, human; D035683:MicroRNAs; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2