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Br J Cancer. 2013 Nov 12;109(10):2636-45. doi: 10.1038/bjc.2013.607. Epub 2013 Oct 3.

Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma.

Author information

1
1] Department of Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan [2] Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

Abstract

BACKGROUND:

Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-29s (miR-29s; miR-29a/b/c) were significantly downregulated in head and neck squamous cell carcinoma (HNSCC) and were putative tumour-suppressive miRNAs in human cancers. Our aim in this study was to investigate the functional significance of miR-29s in cancer cells and to identify novel miR-29s-mediated cancer pathways and responsible genes in HNSCC oncogenesis and metastasis.

METHODS:

Gain-of-function studies using mature miR-29s were performed to investigate cell proliferation, migration and invasion in two HNSCC cell lines (SAS and FaDu). To identify miR-29s-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-29s target genes.

RESULTS:

Restoration of miR-29s in SAS and FaDu cell lines revealed significant inhibition of cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that miR-29s modulated the focal adhesion pathway. Moreover, laminin γ2 (LAMC2) and α6 integrin (ITGA6) genes were candidate targets of the regulation of miR-29s. Luciferase reporter assays showed that miR-29s directly regulated LAMC2 and ITGA6. Silencing of LAMC2 and ITGA6 genes significantly inhibited cell migration and invasion in cancer cells.

CONCLUSION:

Downregulation of miR-29s was a frequent event in HNSCC. The miR-29s acted as tumour suppressors and directly targeted laminin-integrin signalling. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and metastasis and suggests novel therapeutic strategies for the disease.

PMID:
24091622
PMCID:
PMC3833206
DOI:
10.1038/bjc.2013.607
[Indexed for MEDLINE]
Free PMC Article

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