Abstract 152: MicroRNAs in head and neck squamous cell carcinoma

Abstract

Abstract Background: The accumulating evidence indicates that microRNAs play a key role in tumor development and progression. The aim of this study is to assess the role and function of microRNAs in head and neck squamous cell carcinoma. Method and Results: We investigated expression profiles of microRNA in head and neck squamous cell carcinoma by using a miRNA microarray platform. Profiles from tumor samples (n=10) and nontumor tissues (n=10) were compared. We identified 24 differentially expressed miRNAs, of which 1 was significantly downregulated, while the other 23 were upregulated in tumor tissues. Mir-21 was most notably upregulated in tumor tissues (P=0.0002), and mir-375 was a potential tumor suppressive microRNA that was significantly downregulated in tumors (P=0.0002). Expression profiles of these two microRNAs were validated by qRT-PCR with separate clinical samples (16 tumors and 15 normal tissues). In vitro assays confirmed that mir-21 stimulated cell growth and mir-375 had a tumor suppressive role. Next, to assess downstream target genes, cells were subjected to microarray analysis after transient transfection with each microRNA or its negative control. We also conducted a bioinformatics search (TargetScan, PicTar, miRanda). By combining these data, we identified potential target genes including YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide) for mir-375 and BNC2 (Basonuclin 2) for mir-21. These potential target genes were downregulated after forced expression of mir-375 or mir-21. The activities of a luciferase reporter containing these microRNA's binding sequences at the 3’ untranslated region (UTR) of some potential target mRNAs were repressed by the ectopic expression of miR-375 or miR-21, suggesting that some of these candidates are specific targets of these microRNAs. Conclusions: Mir-21 is a potential oncogenic microRNA, and miR-375 is a potential tumor-suppressive microRNA in head and neck squamous carcinoma. Further investigation including pathway analysis of these microRNAs may lead to the detection of therapeutic targets of head and neck cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 152. doi:10.1158/1538-7445.AM2011-152