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Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways
Citation:
JARDIM, M. J., C. Fry, I. JASPERS, L. A. DAILEY, AND D. DIAZ-SANCHEZ. Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 117(11):1745-1751, (2009).
Impact/Purpose:
Alteration of miRNA expression profiles by environmental pollutants such as DEP can significantly and quickly modify cellular processes, ultimately leading to disease pathogenesis.
Description:
Background: Particulate matter is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (small noncoding RNAs) have been suggested as important in maintaining the lung in a disease free state through regulation of gene expression. Although many studies have shown aberrant microRNA expression patterns in diseased versus healthy tissue, little is known regarding whether environmental agents can induce such changes. Objectives: We used diesel exhaust particles (DEP), the largest source of emitted airborne PM, to investigate pollutant induced changes in miRNA expression in airway epithelial cells. We tested the hypothesis that DEP exposure can lead to disruption of normal miRNA expression patterns, representing a plausible novel mechanism through which DEP can mediate disease initiation. Methods: Human bronchial epithelial cells were grown at air-liquid interface until they were highly differentiated. Following treatment with 10 ug/cm2 DEP for 24 hours, total RNA was collected and analyzed for miRNA expression using microarray profile analysis and quantitative real-time PCR. Results: We show here that DEP exposure drastically changes the miRNA expression profile in human airway epithelial cells. Thus, 197 out of 313 detectable miRNAs (62.9%) were either up- or down-regulated by 1.5 fold. Computational pathway analysis suggested that this may result in initiation of disease by altering gene expression. Putative targets of 3 of the most altered miRNAs miR-513a-5p, miR-494 and miR-96 pointed to a prominent role in DEP-induced inflammatory responses. Network target analysis of the 12 most highly altered miRNAs revealed that DEP can induce a very strong tumorigenic disease signature. Conclusions: Alteration of miRNA expression profiles by environmental pollutants such as DEP can significantly and quickly modify cellular processes, ultimately leading to disease pathogenesis.
