| RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver Baohong Zhang1 and Xiaoping Pan2 1Department of Biology, East Carolina University, Greenville, North Carolina, USA; 2Department of Chemistry, Western Illinois University, Macomb, Illinois, USA Abstract
Background: Although microRNAs (miRNAs) have been found to play an important role in many biological and metabolic processes, their functions in animal response to environmental toxicant exposure are largely unknown. Objectives: We used hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) , a common environmental contaminant, as a toxicant stressor to investigate toxicant-induced changes in miRNA expression in B6C3F1 mice and the potential mechanism of RDX-induced toxic action. Methods: B6C3F1 mice were fed diets with or without 5 mg/kg RDX for 28 days. After the feeding trials, we isolated RNAs from both brain and liver tissues and analyzed the expression profiles of 567 known mouse miRNAs using microarray and quantitative real-time polymerase chain reaction technologies. Results: RDX exposure induced significant changes in miRNA expression profiles. A total of 113 miRNAs, belonging to 75 families, showed significantly altered expression patterns after RDX exposure. Of the 113 miRNAs, 10 were significantly up-regulated and 3 were significantly down-regulated (p < 0.01) in both mouse brain and liver. Many miRNAs had tissue-specific responses to RDX exposure. Specifically, expression of seven miRNAs was up-regulated in the brain but down-regulated in the liver or up-regulated in the liver but down-regulated in the brain (p < 0.01) . Many aberrantly expressed miRNAs were related to various cancers, toxicant-metabolizing enzymes, and neurotoxicity. We found a significant up-regulation of oncogenic miRNAs and a significant down-regulation of tumor-suppressing miRNAs, which included let-7, miR-17-92, miR-10b, miR-15, miR-16, miR-26, and miR-181. Conclusions: Environmental toxicant exposure alters the expression of a suite of miRNAs. Key words: carcinogenesis, gene regulation, microarray, microRNA, miRNA, qRT-PCR, RDX, toxicant, toxicity, toxicogenomics. Environ Health Perspect 117:231–240 (2009) . doi:10.1289/ehp.11841 available via http://dx.doi.org/ [Online 19 September 2008]
Address correspondence to B. Zhang, Department of Biology, East Carolina University, Greenville, NC 27858 USA. Telephone: (252) 328-2021. Fax: (252) 328-4178. E-mail: zhangb@ecu.edu Supplemental Material is available online at http://www.ehponline.org/members/2008/11841/suppl.pdf We performed the animal treatment experiments at Texas Tech University (TTU) with the support of the Strategic Environmental Research and Development Program. We greatly appreciated the help and support of G. Cobb at the Institute of Environmental and Human Health and the staff at the TTU Animal facility. We also thank S. McConnell at Western Illinois University (WIU) and E. Stellwag and A. Spuches at East Carolina University (ECU) for reviewing and editing the manuscript. This work was supported by ECU New Faculty Research Startup Funds Program, WIU New Faculty Research Startup Funds Program, and WIU University Research Council. The authors declare they have no competing financial interests. Received 22 June 2008 ; accepted 19 September 2008.
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