Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma

Br J Cancer. 2013 Apr 30;108(8):1648-58. doi: 10.1038/bjc.2013.122. Epub 2013 Apr 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Histone Deacetylase 1 / biosynthesis
  • Histone Deacetylase 1 / genetics*
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Male
  • Maxillary Sinus Neoplasms / enzymology
  • Maxillary Sinus Neoplasms / genetics
  • Maxillary Sinus Neoplasms / metabolism
  • Maxillary Sinus Neoplasms / pathology
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Transfection


  • MIRN874 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • HDAC1 protein, human
  • Histone Deacetylase 1