Abstract 4088: Effects of exposure to particulate matter on methylation of miRNA genes coding for miR-21 and miR-222

Abstract

Abstract BACKGROUND: Inhalation of Particulate Matter (PM) and PM metal components has been associated with increased risk of lung cancer. MicroRNAs (miRNAs) are small, non-coding RNAs with an important role in biological activities and are linked to human diseases such as cancer. miRNA expression needs tight regulation, which also takes place at the epigenetic level. miRNAs undergo regulation by DNA methylation in miRNA coding genes, associate with silencing of miRNA expression. Increased expression of miR-21 has been implicated in various processes involved in carcinogenesis, including inhibition of apoptosis, promotion of cell proliferation and stimulation of tumor growth by targeting multiple tumor/metastasis suppressor genes. In cancer cells miR-222 promotes cell proliferation by targetting the cell cycle inhibitor and tumor suppressor p27. AIMS: We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs methylation (miR-222 and miR-21) in 63 workers of an electric-furnace steel plant with well-characterized exposure. METHODS: We measured miR-222 and miR-21 methylation in blood leukocyte RNA obtained from 63 workers on the first day of a workweek (baseline) and after three days of work (post-exposure). Quantitative miRNA methylation analysis was performed through bisulfite PCR Pyrosequencing. We estimated individual exposures to PM1, PM10, coarse particles and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and post-exposure measurements. RESULTS: miR-222 and miR-21 methylation was significantly decreased in post-exposure samples, compared with baseline (post-exposure=60.07±9.38, baseline=63.05±6.38; p=0.013 for miR-222; post-exposure=62.47±6.87, baseline=66.24±6.32; p=0.004 for miR-21). In post-exposure samples, miR-222 methylation was negatively associated with the average exposure to the levels of PM (βstd=-0.012, p=0.03 for PM10, βstd=-0.579, p=0.005 for PM1 and βstd=-0.013, p=0.032 for Coarse) and to the levels of PM metal components (βstd=-111.345, p=0.008 for Chromium and βstd=17.195, p=0.023 for Arsenic). CONCLUSIONS: Changes in miRNA methylation may represent a novel epigenetic mechanism mediating responses to PM and its metal components. Whether these modifications have a role in the initiation and progression of cancer needs to be evaluated in future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4088.