In 2018, 154,100 lung cancer deaths are projected to occur in the United States. Currently, there are very few predictors to identify lung cancer in its early stages. Recent studies have demonstrated a link between microRNAs (miRNAs) and specific cancers. Dysregulation of miRNAs in cancer can lead to upregulate oncogenes and downregulate tumor suppressors. Previously, we developed a line of transgenic mice expressing the human mutant p53 (273H) gene. The transgenic mice were observed to have accelerated risk of spontaneous adenocarcinomas at the age of 13-14 months. However the mechanisms involved in lung tumorigenesis at this age cohort is still unclear. Herein, we report our analysis on miRNA expression in lung tissue between a low risk cohort and high risk cohort. To investigate the role of mutant p53 in lung tumorigenesis, a p53(273H) transgenic mouse model was developed. Murine lung tissue were harvested from age groups of 7 months (low risk group with risk of 5% of lung cancer), and the 13.5 months (high risk group with risk of 27% of lung cancer). RNA was then extracted with trizol, and miRNAs were quantified using a Nanostring counter miRNA array. The miRNA expressions were normalized and averaged. The normalized miRNAs from high risk group (n=3) were compared with the miRNAs obtained from the low risk group (n=3). We screened 600 different miRNA expressions from these age cohorts. Total of 19 miRNAs that had an up-regulation of at least 5-fold in the high risk cohort as compared with the low risk cohort including some important miRNAs in human lung cancer (e.g mmu-miR-2133, mmu-miR-2140, mmu-miR-142-5p, mmu-miR-2138, mmu-miR-2134, mmu-miR-2135, mmu-miR-452, mmu-miR-703, mmu-miR-690, mmu-miR-206, mmu-miR-706, mmu-miR-691, mmu-miR-208a, mmu-miR-574-5p, mmu-miR-1). Four miRNAs had a down regulation at least 5-fold in the high risk cohort including mmu-miR-720, mmu-miR-1937c, and mmu-miR-1937a+mmu-miR-1937b.We found a group of microRNAs to be expressed abnormally high and another group microRNA to be expressed abnormally low in the high risk group as comparing to the low risk group. We compared the data to our murine lung cancer microRNA profile and found a group of miRNA expression potentially correlated to risk of lung cancer development in mice. Most human lung cancers are at an advanced stage when they are first found. These cancers are very hard to cure. However, if a lung cancer is found at an earlier stage when it is small and before it has spread, the early stage lung cancer can be successfully treated. Further studies are necessary to employ these miRNAs as early diagnostic biomarkers in prediction of human lung cancers.

Citation Format: Myia Aiges, Abeer Almiman, Li Gao, Kathleen Dotts, Miguel A. Villalona-Calero, Wenrui Duan. Differential miRNA expression levels and risk of lung adenocarcinoma in transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3548.