Abstract 2733: K14-GFP-miR-31 transgenic mice confer high susceptibility to squamous cell tumorigenesis on oral tongue and esophagus.

Abstract

Abstract Squamous cell carcinoma (SCC) occurring on head and neck region and esophagus causes tremendous cancer mortality around the world. Effects from tobacco and/or alcoholic carcinogens and other factors are highly associated with the prevalence of these malignancies. MiRNAs are small non-coding RNAs mediating the RNA interference on targeted mRNAs. They play important roles in the pathogenesis of malignancies. miR-31 is among the most eminently up-regulated miRNAs in SCC occurring in head and neck region and esophagus. To elucidate the molecular pathogenesis of SCC, we established miR-31 transgenic mouse lines, in which miR-31 is under the control of K14 promoter and co-expressed with GFP. GFP and miR-31 were detected in basal and suprabasal squamous cells of skin, oral cavity and esophagus in these transgenic mice. The transgenic mice exhibited higher potential for tumor induction than wild type mice on oral tongue and esophagus by 4-nitroquinoline 1-oxide (4NQO) treatment. The precancerous lesions on oral tongues and esophagus in transgenic mice were also in more advanced stages in contrast to counterparts of wild type mice. Homozygous transgenic mice had the worst prognosis than the others. 4NQO induction also up-regulated miR-31 expression in tumors of wild type mice. The tumors induced in transgenic mice expressed more abundant miR-31 and VEGF, and less abundance of factor inhibiting HIF (FIH) than tumors in wild type mice. Base excision repair genes were validated as targets of miR-31 in human SCC cell lines, and the expression of these target genes were also decreased in the squamous epithelium of transgenic mice. This study identifies the high sensitivity of K14-GFP-miR-31 transgenic mice for chemical carcinogen-induced squamous cell tumorigenesis, and this could be associated with the down-regulation of tumor suppressor genes and the impairment of repair activity to counteract carcinogenic stimuli in squamous cells. Citation Format: Ssu-Hsueh Tseng, Yong-Syu Lee, Kuo-Wei Chang, Shu-Chun Lin. K14-GFP-miR-31 transgenic mice confer high susceptibility to squamous cell tumorigenesis on oral tongue and esophagus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2733. doi:10.1158/1538-7445.AM2013-2733