ALTERATION OF microRNA PROFILES IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK CELL LINES BY HUMAN PAPILLOMAVIRUS

Background. Human papillomavirus (HPV)-positive cases of squamous cell carcinoma of the head and neck (SCCHN) have a much better disease outcome compared to SCCHN cases lacking HPV. Differences in microRNA (miRNA) expression may affect their clinical outcomes. Methods. The miRNA expression was studied using micro-arrays and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in HPV-16-positive and HPV-negative SCCHN cell lines. The role of HPV-16 E6 and E7 oncogenes in altering miRNA expression was investigated using human foreskin keratinocytes (HFKs). Results. The miRNAs miR-363, miR-33, and miR-497 were upregulated, whereas miR-155, miR-181a, miR-181b, miR-29a, miR-218, miR-222, miR-221, and miR-142-5p were downregulated in HPV-positive cells compared to both HPV-negative SCCHN and normal oral keratinocytes. HPV-16 E6 oncogene altered miRNA expression in HFKs and in an HPV-16-positive cell line with E6 knockdown using siRNA. Conclusion. miRNAs differentially expressed in the presence of HPV-16 may provide biomarkers for SCCHN and identify cellular pathways targeted by this virus. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 504-512, 2011