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American Head & Neck Society
July 21-25, 2012
Metro Toronto Convention Centre
Toronto, ON, Canada


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THE ROLE OF MICRORNAS IN THE MALIGNANT TRANSFORMATION OF SINONASAL INVERTED PAPILLOMA

Presentation: P160
Topic: Basic Science
Type: Poster
Date: Sunday - Tuesday, July 22 - 24, 2012
Session: Designated Poster viewing times
Authors: Hiromitsu Hatakeyama, MD PhD, Yuji Nakamaru, MD PhD, Akihiro Homma, MD PhD, Nobuhiko Oridate, MD PhD, Takatsugu Mizumati, MD PhD, Satoshi Kano, MD PhD, Satoshi Fukuda, MD PhD, Seigo Suzuki, MD PhD, Tomohiro Sakashita, MD
Institution(s): Hokkaido University

Background: Inverted papilloma(IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses with infection of human papilloma virus(HPV). But these tumor can undergo malignant transformation to squamous cell carcinoma and the role of microRNA s(miRNA) in carcinogenesis remains obscure. In this study, we investigated whole miRNA profiles using the samples in the same patient with IP and SCC to detect the function of miRNA in carcinogenesis of IP.
Experimental design: More than 600 types of miRNA expressions were quantified using TaqMan Low Density Array (TLDA) card which based on RT-PCR. miRNA expressed in more than 80% samples were used for this analysis. All data were normalized by internal control and analyzed with DataAssist software. Expression of molecular targeted by miRNA were estimated with immunostaining.
Results: Total 14 samples were used for this analysis, including 4 FFPE samples of normal nasal epithelium, 5 of IP and 5 of SCC. Unsupervised clustering analysis showed that miRNA-expression signature in IP were similar to SCC, but were totally different from the signature of normal epithelium. Differences by the type of tissue was greater than the individual differences. Although a small difference between IP and SCC, some miRNAs showed big difference. miR-892b showed biggest difference and down-regulated in SCC but we could not confirm the difference in the expression of targeted gene as estrogen receptor gamma. miR-296 was drastically up-regulated in SCC with more than 20 fold difference and targeted p21WAF1 and PTEN. And the expression of molecular including in p21WAF1-p53 pathways were confirmed by immunostaining.
Conclusion: Our results suggested that there were drastic changes in miRNA expression signature through the transition to papilloma. Not all gene were controlled by miRNAs, miR-296 may play a important role in malignant transformation of IP via inhibition of p53-p21WAF1 pathways and be a new agent for cancer prevention.


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