Early and late effects of aspirin and naproxen on microRNAs in the lung and blood of mice, either unexposed or exposed to cigarette smoke
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Alberto Izzotti1,2, Roumen Balansky3, Gancho Ganchev3, Marietta Iltcheva3, Mariagrazia Longobardi1, Alessandra Pulliero1, Anna Camoirano1, Francesco D'Agostini1, Marta Geretto1, Rosanna T. Micale1, Sebastiano La Maestra1, Mark Steven Miller4, Vernon E. Steele4 and Silvio De Flora1
1Department of Health Sciences, University of Genoa, Genoa, Italy
2IRCCS AOU San Martino IST, Genoa, Italy
3National Center of Oncology, Sofia, Bulgaria
4Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
Silvio De Flora, email: [email protected]
Keywords: lung microRNA, blood microRNA, lung carcinogenesis, cigarette smoke, anti-inflammatory drugs
Received: March 07, 2017 Accepted: July 18, 2017 Published: August 24, 2017
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.
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