Abstract 1338: MicroRNAs in a mouse model of oral carcinogenesis

Abstract

Abstract MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes. Aberrant expression of microRNAs has been reported in human tongue squamous carcinoma cells. In this study, we investigated the effects of the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), on the expression of several miRNAs in mouse tongues by using a seminal mouse model of oral carcinogenesis that was established by our laboratory and demonstrates similarities to human oral tumors in terms of morphological, histopathological, and molecular characteristics. In addition, we studied the effects of the DNA methyltransferase (Dnmt) inhibitor 5-Aza-2′-deoxycytidine (5-Aza, 0.25 mg/kg body weight), all-trans retinoic acid (RA, given at 100 μg/kg body weight and 1 mg/kg body weight, respectively), and the combination of 5-Aza and the low dose RA on murine oral cavity carcinogenesis induced by 4-NQO and on mouse tongue miRNA expression levels in this mouse model. Compared with control mice (not treated with 4-NQO), 4-NQO treatment caused a remarked reduction in the expression of miR-26a and miR-124a in mouse tongues and an increase in CDK2 (one of miR-124a's targets) mRNA expression. Among all drug treatments, the combination of 5-Aza and the low dose RA attenuated the reduction in the expression of miR-124a caused by the 4-NQO treatment. To some extent, mice in all drug treatment groups showed a reduction in the degree of decrease in the expression of miR-26a in mouse tongues induced by 4-NQO. These results correlate with the data on neoplastic tongue lesion numbers and tongue lesion severity. Moreover, we found that RA, 5-Aza, and the combination of RA and 5-Aza all enhanced the expression of miR-26a and miR-124a in a human tongue squamous cell carcinoma cell line, SCC-15, and that the combination of RA and 5-Aza had the greatest effects. Collectively, our results show that miRNAs have potential as a strategy to reduce oral cavity 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 1338. doi:10.1158/1538-7445.AM2011-1338