Abstract 18874: A microRNA Signature of Tobacco Exposure
BACKGROUND: Smoking is a cardinal risk factor for cardiovascular disease, and microRNAs (miRNAs) are key regulators of gene expression that may be involved in the development of smoking-related diseases. We sought to unravel the relationship between miRNAs and smoking by describing a miRNA signature of tobacco exposure and relating these results to the expression of smoking-associated genes.
METHODS: Expression profiling of 333 miRNAs was conducted on whole blood RNA from 5,728 Framingham Heart Study participant samples using TaqMan assays and high-throughput qRT-PCR. Smoking status was classified as current, former, or never. The association of miRNA expression with smoking status was tested using general linear models, and significant miRNAs were analyzed in pairwise comparisons. Smoking-related mRNA expression associations were identified from gene expression profiling of the same RNA samples with the Affymetrix Human Exon Array ST v1.0. MiRNA-mRNA coexpression was analyzed using linear mixed effects models.
RESULTS: Seven miRNAs were associated with smoking status: miR-1180, miR-181a2-3p, miR-423-5p, miR-25-5p, miR-1285-3p, miR-342-5p, and miR-744-3p (Table 1). 1,626 gene transcripts were coexpressed with one or more smoking-related miRNAs. Gene ontology enrichment analysis implicated the coexpressed genes in multiple biological processes, e.g., the ubiquitin cycle, intracellular transport, and DNA metabolism. Four genes were coexpressed with all seven smoking-associated miRNAs; most notable were TMEM56, reported to be associated with coronary heart disease, and DOCK8, which has been linked to lung cancer in vitro.
CONCLUSIONS: We identified a novel miRNA signature of tobacco exposure featuring decreased expression of miRNAs in smokers. Our coexpression results implicate these miRNAs in smoking-related diseases and suggest broad regulatory effects on protein synthesis and turnover.
TABLE 1. miRNA Associations with Smoking Status
Author Disclosures: C. Willinger: None. J. Rong: None. T. Huan: None. K. Tanriverdi: None. P. Courchesne: None. J. Dupuis: None. G. O’Connor: None. J. Freedman: None. M.G. Larson: None. D. Levy: None.
- © 2014 by American Heart Association, Inc.