ABSTRACT: While microRNAs have extensively been investigated in cancer research, little is known regarding their response to noxious agents in apparently healthy tissues. We analyzed the expression of 484 miRNAs in the lung of rats exposed to environmental cigarette smoke (ECS) for 28 days. ECS downregulated 126 miRNAs (26.0%) at least two-fold and 24 miRNAs more than three-fold. We previously demonstrated that 107 of 4858 genes (2.9%) and 50 of 518 proteins (9.7%) were upregulated by ECS in the same tissue, consistently with the role of microRNAs as negative regulators of gene expression. The most remarkably downregulated microRNAs belonged to the families of let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR- 122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223, which regulate stress response, apoptosis, proliferation, angiogenesis, and expression of genes. In contrast, miR-294, an inhibitor of transcriptional repressor genes, was upregulated by ECS. There was a strong parallelism in dysregulation of rodent microRNAs and their human homologues, which are often transcribed from genes localized in fragile sites deleted in lung cancer. Five ECS-downregulated microRNAs are known to be affected by single nucleotide polymorphisms. Thus, changes in microRNA expression are an early event following exposure to cigarette smoke. Keywords: microRNAs • gene expression • environmental cigarette smoke
