Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas.
OBJECTIVE
The objective of this study is to investigate the significance of microRNAs (miRNA) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).


METHODS
A global miRNA profiling was done on 51 formalin-fixed archival HNSCC samples using quantitative reverse transcription-PCR approach, correlated with patients' clinical parameters. Functional characterization of HNSCC-associated miRNAs was conducted on three HNSCC cell lines. Cell viability and proliferation were investigated using MTS and clonogenic assays, respectively; cell cycle analyses were assessed using flow cytometry.


RESULTS
Thirty-eight of the 117 (33%) consistently detected miRNAs were significantly differentially expressed between malignant versus normal tissues. Concordant with previous reports, overexpression of miR-21, miR-155, let-7i, and miR-142-3p and underexpression of miR-125b and miR-375 were detected. Upregulation of miR-423, miR-106b, miR-20a, and miR-16 as well as downregulation of miR-10a were newly observed. Exogenous overexpression of miR-375 in HNSCC cell lines reduced proliferation and clonogenicity and increased cells in sub-G(1). Similar cellular effects were observed in knockdown studies of the miR-106b-25 cluster but with accumulation of cells in G(1) arrest. No major difference was detected in miRNA profiles among laryngeal, oropharyngeal, or hypopharyngeal cancers. miR-451 was found to be the only significantly overexpressed miRNA by 4.7-fold between nonrelapsed and relapsed patients.


CONCLUSIONS
We have identified a group of aberrantly expressed miRNAs in HNSCC and showed that underexpression of miR-375 and overexpression of miR-106b-25 cluster might play oncogenic roles in this disease. Further detailed examinations of miRNAs will provide opportunities to dissect the complex molecular abnormalities driving HNSCC progression.
Division of Applied Molecular Oncology, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Angela B Y
AB
Hui
Michelle
M
Lenarduzzi
Tiffaney
T
Krushel
Levi
L
Waldron
Melania
M
Pintilie
Wei
W
Shi
Bayardo
B
Perez-Ordonez
Igor
I
Jurisica
Brian
B
O'Sullivan
John
J
Waldron
Pat
P
Gullane
Bernard
B
Cummings
Fei-Fei
FF
Liu
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D014162:Transfection
D035683:MicroRNAs