Details

Autor(en) / Beteiligte

• HUI, Angela B. Y
• LENARDUZZI, Michelle
• GULLANE, Pat
• CUMMINGS, Bernard
• LIU, Fei-Fei
• KRUSHEL, Tiffaney
• WALDRON, Levi
• PINTILIE, Melania
• WEI SHI
• PEREZ-ORDONEZ, Bayardo
• JURISICA, Igor
• O'SULLIVAN, Brian
• WALDRON, John

Titel

Comprehensive MicroRNA Profiling for Head and Neck Squamous Cell Carcinomas

Ist Teil von

• Clinical cancer research, 2010-02, Vol.16 (4), p.1129-1139

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose: 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). Experimental Design: 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. Conclusion: 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. Clin Cancer Res; 16(4); 1129–39