文章基本信息

标题：Formaldehyde and Epigenetic Alterations: MicroRNA Changes in the Nasal Epithelium of Nonhuman Primates
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作者：Julia E. Rager ; Benjamin C. Moeller ; Melanie Doyle-Eisele 等
期刊名称：Environmental Health Perspectives
印刷版ISSN：0091-6765
电子版ISSN：1552-9924
出版年度：2013
卷号：121
期号：3
页码：339-344
DOI：10.1289/ehp.1205582
出版社：OCR Subscription Services Inc
摘要：a c k g r o u n d: Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiq uito us nature, it is impera tive to understa nd the mechanisms underlying formaldehyde- induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde. Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disrup-tions in miRNA expression profiles in vitro.oB j e c t i v e s: Using an in vivo model, we set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates.Me t h o d s: Cynomolgus macaques were exposed by inhalation to approximately 0, 2, or 6 ppm formaldehyde for 6 hr/day for 2 consecutive days. Small RNAs were extracted from nasal samples and assessed for genome-wide miRNA expression levels. Transcriptional targets of formaldehyde-altered miRNAs were computationally predicted, analyzed at the systems level, and assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR).re s u l t s: Expression analysis revealed that 3 and 13 miRNAs were dysregulated in response to 2 and 6 ppm formaldehyde, respectively. Transcriptional targets of the miRNA with the greatest increase (miR-125b) and decrease (miR-142-3p) in expression were predicted and analyzed at the systems level. Enrichment was identified for miR-125b targeting genes involved in apoptosis signaling. The apoptosis- related targets were functionally tested using RT-PCR, where all targets showed decreased expression in formaldehyde- exposed samples.co n c l u s i o n s: Formaldehyde exposure significantly disrupts miRNA expression profiles within the nasal epithelium, and these alterations likely influence apoptosis signaling
关键词：apoptosis; epigenetics; formaldehyde; microRNA; primate; systems biology