Abstract 3130: Discovery of tumor suppressor microRNA using smoking-related lung carcinogenesis cell model

Abstract

Abstract Cigarette smoking is an important risk factor for lung cancer and induces DNA hypermethylation. Hypermethylation can silence tumor suppressor miRNAs. However, it is less known regarding the role of miRNA methylation in lung carcinogenesis, especially smoking-related lung cancer. We are now to discover the smoking-induced altered tumor suppressor miRNA in human lung carcinogenesis cell model. First, we examined miRNA expression profiles using Affymetrix GeneChip miRNA4.0 in human lung carcinogenesis cell model; NHBE, BEAS2B, 1799, 1198, 1170I cells (PNAS. 89:6693-97. 1992, Cancer Biol Ther. 5:665-73. 2006). And we have validated candidate tumor suppressor miRNAs by TaqMan real time PCR. We first discovered 6 candidate tumor suppressor miRNAs (miR-4448, miR-3180-3p, miR-584-5p, miR-3658, miR-8064, miR-371b) and we confirmed known decreased expression of several miRNAs in lung carcinogenesis cell model. Next, we tested methylation of candidate tumor suppressor miRNAs promoter CpG site by pyrosequencing. Increase of methylation was observed for 4 of the 6 candidate tumor suppressor miRNAs in human lung carcinogenesis cell model. Furthermore, methylation of miR-584-5p, miR-3658, miR-8064, miR-371b were greater in 1198 and 1170I cells exposed to cigarette smoking condensate (CSC). In the further study, we will confirm the role of tumor suppressor miRNA in smoking-related lung carcinogenesis by functional study. These finding suggest that tumor suppressor miRNAs are miRNA silenced by epigenetic mechanisms during smoking-induced lung carcinogenesis. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2062146) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI13C1611). Citation Format: Jae Sook Sung, Jong Won Lee, Yeul Hong Kim. Discovery of tumor suppressor microRNA using smoking-related lung carcinogenesis cell 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 3130. doi:10.1158/1538-7445.AM2015-3130