title: miR-494 represses HOXA10 expression and inhibits cell proliferation in oral cancer.
abstract: OBJECTIVE
  miR-494 was identified as a candidate of the most significantly underexpressed microRNAs (miRNAs) in our oral cancer screen. The aim of this study was to validate whether miR-494 has a functional role in oral cancer.
  
  
  METHODS
  Quantitative miRNA analyses were performed on oral tumor RNA and oral cancer cell lines. HOXA10 was selected for further analysis based on bioinformatics analysis of miR-494 targets and a previous report of overexpression of HOXA10 in oral cancer. Transient transfection of miRNA-mimic and inhibitor were performed in SCC-25 (tongue), CAL 27 (tongue), and FaDu (pharynx) cancer cells and regulation of HOXA10 by miR-494 was investigated. Dual luciferase assay was used to verify the interaction between miR-494 and HOXA10 in reporter cells. The effect of miR-494 on cell proliferation was examined.
  
  
  RESULTS
  Our data showed that miR-494 was underexpressed whereas HOXA10 was overexpressed in oral cancer compared to normal tissues. An inverse correlation between miR-494 and HOXA10 was observed in the human tissues (p<0.05). Transient transfection of miR-494 in all cancer cell lines significantly reduced the expression of HOXA10 mRNA. The luciferase reporter that contains the 3'UTR of HOXA10 showed a significantly reduced luciferase activity by miR-494 indicating a direct interaction between HOXA10 and miR-494. Significant reduction in cell proliferation was demonstrated in tongue cancer cells transfected with miR-494.
  
  
  CONCLUSIONS
  miR-494 repressed the expression of HOXA10 and also reduced the proliferation of oral cancer cells. These data give more evidence of the role of miR-494 as a tumor suppressor miRNA in oral cancer.
authors.affiliation: Department of Oral Biology, University of Florida, P.O. Box 100424, Gainesville, FL 32610-0424, USA; Department of Pathology and Legal Medicine, Federal University of Amazonas, Av. Valdemar Pedrosa, 1097, CEP 69020-160 AM, Brazil. Electronic address: tliborio@ufam.edu.br.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Libório-Kimura
authors.affiliation: Department of Oral Biology, University of Florida, P.O. Box 100424, Gainesville, FL 32610-0424, USA. Electronic address: hyunmin.jung@nih.gov.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Jung
authors.affiliation: Department of Oral Biology, University of Florida, P.O. Box 100424, Gainesville, FL 32610-0424, USA. Electronic address: echan@ufl.edu.
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C547168:MIRN494 microRNA, human; D035683:MicroRNAs; C069634:HOXA10 protein, human
keywords: HOXA10; MicroRNA; Oral cancer; miR-375; miR-494