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Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature
- Source :
- British Journal of Cancer
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Background: Hypopharyngeal squamous cell carcinoma (HSCC) has a very poor prognosis because of its high rates of regional and distant metastasis. Identification of differentially expressed miRNAs and their regulated molecular targets in tumour cells might enhance our understanding of the molecular mechanisms of metastasis in human cancers. Methods: A HSCC miRNA signature was constructed by array-based methods. Functional studies of microRNA-451a (miR-451a) and target genes were performed to investigate cell proliferation, migration and invasion by cancer cell lines. To identify miR-451a-regulated molecular targets, we adopted gene expression analysis and in silico database analysis. Results: Our miRNA signature revealed that miR-451a was significantly downregulated in HSCC. Restoration of miR-451a in cancer cell lines revealed that this miRNA significantly inhibited cancer cell migration and invasion. Our data demonstrated that the gene coding for endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN/DCBLD2) was a direct target of miR-451a regulation. Silencing of ESDN inhibited cell migration and invasion by cancer cells. Conclusions: Loss of tumour suppressive miR-451a enhanced cancer cell migration and invasion in HSCC through direct regulation of ESDN. Our miRNA signature and functional analysis of targets regulated by tumour suppressive miR-451a provide new insights into the potential mechanisms of HSCC oncogenesis and metastasis.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
tumour suppressor
expression signature
Cell Growth Processes
Biology
Transfection
medicine.disease_cause
Metastasis
ESDN/DCBLD2
Cell Line, Tumor
microRNA
medicine
Humans
Gene silencing
Molecular Diagnostics
Aged
hypopharyngeal squamous cell carcinoma
Hypopharyngeal Neoplasms
Squamous Cell Carcinoma of Head and Neck
Cell growth
Gene Expression Profiling
Cell migration
Middle Aged
medicine.disease
miR-451a
Gene Expression Regulation, Neoplastic
Gene expression profiling
MicroRNAs
Oncology
Head and Neck Neoplasms
Cancer cell
Carcinoma, Squamous Cell
Cancer research
Female
Carcinogenesis
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....05acb23ea6e74a7b4efcf256b8821476