Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes

Valentina Bollati, Barbara Marinelli, Pietro Apostoli, Matteo Bonzini, Francesco Nordio, Mirjam Hoxha, Valeria Pegoraro, Valeria Motta, Letizia Tarantini, Laura Cantone, Joel Schwartz, Pier Alberto Bertazzi, Andrea Baccarelli, Valentina Bollati, Barbara Marinelli, Pietro Apostoli, Matteo Bonzini, Francesco Nordio, Mirjam Hoxha, Valeria Pegoraro, Valeria Motta, Letizia Tarantini, Laura Cantone, Joel Schwartz, Pier Alberto Bertazzi, Andrea Baccarelli

Abstract

Background: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level.

Objectives: We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs (miR-222, miR-21, and miR-146a) related with oxidative stress and inflammatory processes in 63 workers at an electric-furnace steel plant.

Methods: We measured miR-222, miR-21, and miR-146a expression in blood leukocyte RNA on the first day of a workweek (baseline) and after 3 days of work (postexposure). Relative expression of miRNAs was measured by real-time polymerase chain reaction. We measured blood oxidative stress (8-hydroxyguanine) and estimated individual exposures to PM1 (< 1 microm in aerodynamic diameter), PM10 (< 10 microm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements.

Results: Expression of miR-222 and miR-21 (using the 2-DeltaDeltaCT method) was significantly increased in postexposure samples (miR-222: baseline = 0.68 +/- 3.41, postexposure = 2.16 +/- 2.25, p = 0.002; miR-21: baseline = 4.10 +/- 3.04, postexposure = 4.66 +/- 2.63, p = 0.05). In postexposure samples, miR-222 expression was positively correlated with lead exposure (beta = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (beta = 0.11, p = 0.03) but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline (baseline = 0.61 +/- 2.42, postexposure = 1.90 +/- 3.94, p = 0.19) but was negatively correlated with exposure to lead (beta = -0.51, p = 0.011) and cadmium (beta = -0.42, p = 0.04).

Conclusions: Changes in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components.

Figures

Figure 1
Figure 1
Dot plots representing baseline and postexposure measures of miR-21 (A), miR-222 (B), and miR-146a (C) expression. Data are represented as −ΔΔCt to approximate the Gaussian distribution; for postexposure compared with baseline, p = 0.0503 for miR-21 (A), p = 0.0024 for miR-222 (B), and p = 0.1917 for miR-146a (C).

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