Downstream functional analysis of miRNA targets (as described in Li et al., 2011) revealed a potential link between the differentially expressed miRNAs and BaP-affected processes such as carcinogenic transformation and angiogenesis in lung tissue. Because each miRNA can regulate several hundred genes, most of which would not be found in the gene expression profile, we also examined the genes that may be regulated by the specific miRNAs but were not differentially expressed. The analysis showed that these genes mainly were

GW-572016 in vivo implicated in gene expression, cellular proliferation, cell death and cancer. Comparison of these results with the BaP-affected predicted targets suggests that immune response was the primary target of BaP via miRNA response. It is known that multiple miRNAs can target the same gene, and that individual miRNAs potentially target many genes. However, the molecular circumstances leading to the selection of a miRNA and its mRNA targets are not well understood. These results suggest that many of the processes NVP-BGJ398 research buy affected by

BaP are generally influenced by miRNAs. Further experimental work is required to decipher the complex role of miRNAs in BaP-induced lung carcinogenesis. Downregulation of B cell receptor signalling is a hallmark feature of many B cell lymphomas including Hodgkin and mantle cell lymphomas. The mRNA and miRNA profiles produced from the lungs of BaP exposed mice revealed striking similarities to the unusual

immunophenotype seen in Hodgkin and mantle cell lymphomas (Savage et al., 2003 and Zhao et al., 2010). Direct experimental evidence showing development of lymphomas in animal models in response to exposure to PAH is scarce. However, Castro et al. (2008) showed that administration of the potent carcinogenic PAH dibenzo(a)pyrene during late gestation results in mortality of pups as a consequence of T-cell lymphoma. The surviving pups develop multiple lung tumours (Castro et al., 2008). Montelukast Sodium BaP caused enhanced susceptibility to lymphomagenesis in mice that are deficient in the DNA mismatch repair gene MSH2 (Zienolddiny et al., 2006). AHR-mediated transcriptional activities also influence the susceptibility of lymphocytes to PAH exposure (Near et al., 1999). Activation of AHR and its resulting effect on transcription led to inhibition of programmed cell death in several lymphoma cell lines and development of lymphoma in superficial lymph nodes in mice treated with TCDD (Vogel et al., 2007). These results suggest that BaP could promote the formation of lymphomas through alteration in the expression of genes regulated by AHR, and that miRNAs may play a major role in this regulation. Our results clearly show that pulmonary miRNAs are more responsive to BaP treatment than hepatic miRNAs.