MicroRNA, environmental carcinogens and risk of lung cancer

摘要: Lung cancer is the leading cause of related deaths world wide. The major lung tobacco smoking. Tobacco smoke contains many different carcinogens including polycyclic aromatic hydrocarbons (PAH), which are known to DNA damage and initiate tumourigenesis. aryl hydrocarbon receptor (AHR) a basic helix-loop-helix protein PER-ARNT-SIM (PAS) family transcription factors, involved in biological processes development, cell cycle regulation, differentiation, cell-cell signalling, cellular growth, circadian rhythms. Most function AHR, however, regarding its role transcriptional induction xenobiotic metabolis- ing enzymes (XMEs). In lung, PAHs bind activate members cytochrome P450 (CYP) enzyme that activation pro-carcinogenic carcinogenic metabolites. MicroRNAs (miRNAs), group short non-coding RNA molecules, mediate sequence specific silencing messenger RNAs (mRNAs) important regulation gene expression. deregula- tion certain miRNAs has been observed several types cancer, cancer. Like mRNAs, belong class II type genes, these can therefore be regulated by same factors. Little environmental toxicology. aim this thesis was identify consequently may mediating toxicity carcinogens. Expression levels 750 mouse Ahr wild-type knockout animals were pro- filed RT-qPCR arrays. Fifteen found differentially expressed between groups, only one up-regulated. pathways studied an bioinformatic approach. Four from experiment, whose expression most significantly divergent, together with three previously reported murine lines, interference (RNAi) experiment immortalised human epithelial lines. Two miRNAs, both selected literature, have altered AHR knockdown cells compared control cells. Discrepancies identified vivo vitro experiments observed. Taken suggest difference effect vitro, rather than differences species. conclusion, it possibly AHR- dependent manner lung. care must taken when extrapolating miRNA data culture studies whole organs or organisms.