Abstract 5355: HPV-16 infection alters cellular microRNA expression in squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Abstract Up to 30% of squamous cell carcinoma of the head and neck (SCCHN) contain human papillomavirus (HPV) type 16 DNA. The presence of HPV DNA in these cancers is associated with a better disease outcome, and an understanding of the differences between HPV-positive and HPV-negative SCCHN has significant clinical importance. MicroRNAs (miRNAs) are approximately 22 nucleotides long, single-stranded RNAs that regulate gene expression at a posttranscriptional level. We hypothesize that HPV infection alters cellular miRNA expression which leads to changes in the expression of their target genes. We investigated the expression of cellular miRNAs using microarrays and quantitative Real Time RT-PCR. We found that 3 miRNAs were upregulated and 8 miRNAs were downregulated in HPV-positive SCCHN cell lines compared to HPV-negative SCCHN cell lines. MiR-363, miR-497, and miR-33 were upregulated, while miR-155, miR-181a, miR-181b, miR-29a, miR-218, miR-222, miR-221, and miR-142-5p were downregulated. We also analyzed miRNA expression in HPV-positive and HPV-negative SCCHN tumors and normal oral tissues. There were 17 up- and 1 downregulated miRNAs in SCCHN tumors compared to normal oral mucosa. These included several miRNAs that are known to be altered in many cancers, such as miR-21, miR-17-5p, and miR-145. MiR-363, the most upregulated miRNA in the HPV-positive cell lines, was also upregulated in HPV-positive tumors compared to HPV-negative tumors. Preliminary data using cell lines expressing HPV-16 E6 and/or E7 oncogene has shown that miR-363 expression increases with the expression of E6. These results suggest a possible role of HPV in altering the expression of specific cellular miRNAs, including miR-363. Studies are currently in progress to identify miR-363 gene targets by utilizing gene expression data and spectral counting proteomics. MiRNAs altered by the presence of HPV may identify specific pathways targeted by the virus, and may provide novel therapeutic targets for HPV-associated SCCHN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5355.