title: Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Our recent studies of microRNA (miRNA) expression signature demonstrated that microRNA-874 (miR-874) was significantly downregulated in maxillary sinus squamous cell carcinoma (MSSCC), and a putative tumour-suppressive miRNA in human cancers. Our aim of this study was to investigate the functional significance of miR-874 in cancer cells and to identify novel miR-874-mediated cancer pathways and responsible genes in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Gain-of-function studies using mature miR-874 were performed to investigate cell proliferation and cell cycle distribution in HNSCC cell lines (SAS and FaDu). To identify miR-874-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-874 target genes.
  
  
  RESULTS
  Expression levels of miR-874 were significantly downregulated in HNSCC tissues (including oral, pharyngeal and laryngeal SCCs) compared with normal counterpart epithelia. Restoration of miR-874 in SAS and FaDu cell lines revealed significant inhibition of cell proliferation and induction of G2/M arrest and cell apoptosis. Our expression data and in silico analysis demonstrated that miR-874 modulated the cell cycle pathway. Moreover, histone deacetylase 1 (HDAC1) was a candidate target of miR-874 regulation. Luciferase reporter assays showed that miR-874 directly regulated HDAC1. Silencing of the HDAC1 gene significantly inhibited cell proliferation and induced G2/M arrest and cell apoptosis in SAS cells.
  
  
  CONCLUSIONS
  Downregulation of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumour suppressor and directly targeted HDAC1. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and suggests novel therapeutic strategies for the disease.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nohata
authors.forename: T
authors.initials: T
authors.lastname: Hanazawa
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: A
authors.initials: A
authors.lastname: Inamine
authors.forename: N
authors.initials: N
authors.lastname: Kikkawa
authors.forename: T
authors.initials: T
authors.lastname: Itesako
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: H
authors.initials: H
authors.lastname: Enokida
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: N
authors.initials: N
authors.lastname: Seki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056284:Histone Deacetylase 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008444:Maxillary Sinus Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: C561946:MIRN874 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
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