Abstract Oral carcinoma is one of the leading causes of cancer death in the world. To develop biomarkers for early detection may bestow substantial benefits in diagnosis and the prevention of tumor progression. An animal model simulating the human pathogenesis will also be useful for developing therapeutic strategies. miRNAs are short, non-coding RNAs, which play important roles in neoplastic process. The detection of biomarkers in body fluid may enable non-invasive diagnostic approaches. This study used mouse chemical carcinogenesis model to investigate the disruption of miRNA expression in oral tongue tissues, and to explore the miRNA level in saliva and blood during pathogenesis. Mice were fed with 4-Nitroquinoline 1-Oxide (4NQO) in drinking water for 12 weeks and were kept for extended periods for tumor induction. The histological examination showed the consecutive increase in the severity of epithelial pathogenesis from hyperkeratosis, hyperplasia to epithelial dysplasia and squamous tumors following the increase of 4NQO exposure. The increase of miR-21 and miR-31 staining, as well as p53, pAKT and Ki-67 immunoreactivity parallels the severity of epithelial pathogenesis in tongue tissues. A progressive increase of multiple oncogenic miRNAs in both saliva and blood samples was also noted. The increase of miR-21, miR-31 and miR-372 in the saliva and the increase of miR-146a and miR-184 in the blood sample were particularly eminent during the field cancerization process of tongue. In addition, the dysregulation of these oncogenic miRNAs and other molecular events in this model are similar to the disruption being identified in human counterparts. As these miRNAs are functionally oncogenic, their increase in the saliva and blood of mice may be valuable biomarkers to develop diagnosis and prevention strategies against oral carcinomas. Keywords: chemical, carcinoma, miRNA, mouse, mouth Note: This abstract was not presented at the meeting. Citation Format: YUYU KAO, Shu-Chun Lin, Kuo-Wei Chang. The increase of oncogenic miRNA expression in tongue carcinogenesis of a mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4000. doi:10.1158/1538-7445.AM2015-4000