We recently showed that nonsteroidal anti-inflammatory drugs (
NSAIDs) are able to inhibit the lung
tumors induced by cigarette
smoke, either mainstream (MCS) or environmental (ECS), in female mice. We used subsets of mice to analyze the expression of 1135
microRNAs in both lung and blood serum, as related to the whole-body exposure to
smoke and/or
oral administration of either
aspirin or
naproxen. In a first study, we evaluated early
microRNA alterations in A/J mice exposed to ECS for 10 weeks, starting at birth, and/or treated with
NSAIDs for 6 weeks, starting after weaning. At that time, when no histopathological change were apparent, ECS caused a considerable downregulation of pulmonary
microRNAs affecting both adaptive mechanisms and disease-related pathways.
Aspirin and
naproxen modulated, with intergender differences, the expression of
microRNAs having a variety of functions, also including regulation of
cyclooxygenases and
inflammation. In a second study, we evaluated late
microRNA alterations in Swiss H mice exposed to MCS during the first 4 months of life and treated with
NSAIDs after weaning until 7.5 months of life, when
tumors were detected in mouse lung. Modulation of pulmonary
microRNAs by the two
NSAIDs was correlated with their ability to prevent preneoplastic lesions (microadenomas) and
adenomas in the lung. In both studies, exposure to
smoke and/or treatment with
NSAIDs also modulated
microRNA profiles in the blood serum. However, their levels were poorly correlated with those of pulmonary
microRNAs, presumably because circulating
microRNAs reflect the contributions from multiple organs and not only from lung.