Interplay Between Cigarette Smoke Exposure, Inflammation, and ADAR-Mediated RNA Editing

Cigarette smoking is a major risk factor for chronic lung diseases, including chronic obstructive pulmonary disease (COPD), and is associated with persistent inflammation and increased cancer risk. Since emerging evidence suggests that modifications of RNA editing levels are associated with a variety of inflammation diseases and cancer, we decided to explore the role of adenosine deaminase acting on RNA (ADAR)-mediated RNA editing in smoking-associated lung inflammation. To address this, whole-transcriptome profiles and protein analysis of smokers and control non-smokers lung tissue samples were analysed and both molecular pathways and the levels of ADAR editing were considered. In parallel, bronchial cell cultures were transfected with pmGFADAR1-p110 or pmGFADAR1-p150, to analyze possible transcriptional changes following ADAR over-expression. RNA sequencing revealed an increase in ADAR1 editing in both smoker lung tissues and ADAR1 transfected bronchial cell cultures, that was confirmed at protein level with Western Blotting analyses. Moreover, a correlation with the overexpression of inflammation-related genes and ADAR editing was found in lung tissue, but not in ADAR1 transfected cell cultures. In conclusion, this study provides a first insight in the role for ADAR1 editing in smoking-associated transcriptional modulation and inflammation.